Evidence for a causal link between sepsis and long-term mortality: a systematic review of epidemiologic studies View Full Text


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Article Info

DATE

2016-04-13

AUTHORS

Manu Shankar-Hari, Michael Ambler, Viyaasan Mahalingasivam, Andrew Jones, Kathryn Rowan, Gordon D. Rubenfeld

ABSTRACT

BACKGROUND: In addition to acute hospital mortality, sepsis is associated with higher risk of death following hospital discharge. We assessed the strength of epidemiological evidence supporting a causal link between sepsis and mortality after hospital discharge by systematically evaluating the available literature for strength of association, bias, and techniques to address confounding. METHODS: We searched Medline and Embase using the following 'mp' terms, MESH headings and combinations thereof - sepsis, septic shock, septicemia, outcome. Studies published since 1992 where one-year post-acute mortality in adult survivors of acute sepsis could be calculated were included. Two authors independently selected studies and extracted data using predefined criteria and data extraction forms to assess risk of bias, confounding, and causality. The difference in proportion between cumulative one-year mortality and acute mortality was defined as post-acute mortality. Meta-analysis was done by sepsis definition categories with post-acute mortality as the primary outcome. RESULTS: The literature search identified 11,156 records, of which 59 studies met our inclusion criteria and 43 studies reported post-acute mortality. In patients who survived an index sepsis admission, the post-acute mortality was 16.1% (95% CI 14.1, 18.1%) with significant heterogeneity (p < 0.001), on random effects meta-analysis. In studies reporting non-sepsis control arm comparisons, sepsis was not consistently associated with a higher hazard ratio for post-acute mortality. The additional hazard associated with sepsis was greatest when compared to the general population. Older age, male sex, and presence of comorbidities were commonly reported independent predictors of post-acute mortality in sepsis survivors, challenging the causality relationship. Sensitivity analyses for post-acute mortality were consistent with primary analysis. CONCLUSIONS: Epidemiologic criteria for a causal relationship between sepsis and post-acute mortality were not consistently observed. Additional epidemiologic studies with recent patient level data that address the pre-illness trajectory, confounding, and varying control groups are needed to estimate sepsis-attributable additional risk and modifiable risk factors to design interventional trials. More... »

PAGES

101

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    http://scigraph.springernature.com/pub.10.1186/s13054-016-1276-7

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    http://dx.doi.org/10.1186/s13054-016-1276-7

    DIMENSIONS

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    https://www.ncbi.nlm.nih.gov/pubmed/27075205


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    29 schema:description BACKGROUND: In addition to acute hospital mortality, sepsis is associated with higher risk of death following hospital discharge. We assessed the strength of epidemiological evidence supporting a causal link between sepsis and mortality after hospital discharge by systematically evaluating the available literature for strength of association, bias, and techniques to address confounding. METHODS: We searched Medline and Embase using the following 'mp' terms, MESH headings and combinations thereof - sepsis, septic shock, septicemia, outcome. Studies published since 1992 where one-year post-acute mortality in adult survivors of acute sepsis could be calculated were included. Two authors independently selected studies and extracted data using predefined criteria and data extraction forms to assess risk of bias, confounding, and causality. The difference in proportion between cumulative one-year mortality and acute mortality was defined as post-acute mortality. Meta-analysis was done by sepsis definition categories with post-acute mortality as the primary outcome. RESULTS: The literature search identified 11,156 records, of which 59 studies met our inclusion criteria and 43 studies reported post-acute mortality. In patients who survived an index sepsis admission, the post-acute mortality was 16.1% (95% CI 14.1, 18.1%) with significant heterogeneity (p < 0.001), on random effects meta-analysis. In studies reporting non-sepsis control arm comparisons, sepsis was not consistently associated with a higher hazard ratio for post-acute mortality. The additional hazard associated with sepsis was greatest when compared to the general population. Older age, male sex, and presence of comorbidities were commonly reported independent predictors of post-acute mortality in sepsis survivors, challenging the causality relationship. Sensitivity analyses for post-acute mortality were consistent with primary analysis. CONCLUSIONS: Epidemiologic criteria for a causal relationship between sepsis and post-acute mortality were not consistently observed. Additional epidemiologic studies with recent patient level data that address the pre-illness trajectory, confounding, and varying control groups are needed to estimate sepsis-attributable additional risk and modifiable risk factors to design interventional trials.
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    37 MEDLINE
    38 MP
    39 MeSH headings
    40 acute hospital mortality
    41 acute mortality
    42 acute sepsis
    43 addition
    44 additional epidemiologic studies
    45 additional hazard
    46 additional risk
    47 admission
    48 adult survivors
    49 age
    50 analysis
    51 arm comparison
    52 association
    53 authors
    54 available literature
    55 bias
    56 categories
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    58 causal relationship
    59 causality
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    62 comorbidities
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    64 confounding
    65 control arm comparisons
    66 control group
    67 criteria
    68 data
    69 data extraction form
    70 death
    71 definition categories
    72 differences
    73 discharge
    74 effect
    75 epidemiologic criteria
    76 epidemiologic studies
    77 epidemiological evidence
    78 evidence
    79 extraction form
    80 factors
    81 form
    82 general population
    83 group
    84 hazard ratio
    85 hazards
    86 headings
    87 heterogeneity
    88 high risk
    89 higher hazard ratio
    90 hospital discharge
    91 hospital mortality
    92 inclusion criteria
    93 independent predictors
    94 index sepsis admission
    95 interventional trials
    96 level data
    97 link
    98 literature
    99 literature search
    100 long-term mortality
    101 male sex
    102 modifiable risk factors
    103 mortality
    104 non-sepsis control arm comparisons
    105 older age
    106 one-year mortality
    107 one-year post-acute mortality
    108 outcomes
    109 patient-level data
    110 patients
    111 population
    112 post-acute mortality
    113 pre-illness trajectory
    114 predictors
    115 presence
    116 presence of comorbidities
    117 primary analysis
    118 primary outcome
    119 proportion
    120 random effects
    121 ratio
    122 recent patient level data
    123 records
    124 relationship
    125 review
    126 risk
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    128 risk of bias
    129 search
    130 sensitivity analysis
    131 sepsis
    132 sepsis admission
    133 sepsis definition categories
    134 sepsis survivors
    135 sepsis-attributable additional risk
    136 septic shock
    137 septicemia
    138 sex
    139 shock
    140 significant heterogeneity
    141 strength
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    143 study
    144 survivors
    145 systematic review
    146 technique
    147 terms
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