Rate and risk factors for rehospitalisation in sepsis survivors: systematic review and meta-analysis

Abstract

Purpose: Sepsis survivors have a higher risk of rehospitalisation and of long-term mortality. We assessed the rate, diagnosis, and independent predictors for rehospitalisation in adult sepsis survivors.

Methods: We searched for non-randomized studies and randomized clinical trials in MEDLINE, Cochrane Library, Web of Science, and EMBASE (OVID interface, 1992-October 2019). The search strategy used controlled vocabulary terms and text words for sepsis and hospital readmission, limited to humans, and English language. Two authors independently selected studies and extracted data using predefined criteria and data extraction forms.

Results: The literature search identified 12,544 records. Among 56 studies (36 full and 20 conference abstracts) that met our inclusion criteria, all were non-randomised studies. Studies most often report 30-day rehospitalisation rate (mean 21.4%, 95% confidence interval [CI] 17.6-25.4%; N = 36 studies reporting 6,729,617 patients). The mean (95%CI) rehospitalisation rates increased from 9.3% (8.3-10.3%) by 7 days to 39.0% (22.0-59.4%) by 365 days. Infection was the most common rehospitalisation diagnosis. Risk factors that increased the rehospitalisation risk in sepsis survivors were generic characteristics such as older age, male, comorbidities, non-elective admissions, hospitalisation prior to index sepsis admission, and sepsis characteristics such as infection and illness severity, with hospital characteristics showing inconsistent associations. The overall certainty of evidence was moderate for rehospitalisation rates and low for risk factors.

Conclusions: Rehospitalisation events are common in sepsis survivors, with one in five rehospitalisation events occurring within 30 days of hospital discharge following an index sepsis admission. The generic and sepsis-specific characteristics at index sepsis admission are commonly reported risk factors for rehospitalisation.

Registration: PROSPERO CRD 42016039257, registered on 14-06-2016.

Keywords: Competing risk; Rehospitalisation; Risk factors; Sepsis.

Fig. 1

PICO summary and approach to research question. The principal exposure was surviving an index sepsis-related hospitalisation (sepsis survivors). The outcome of interest was all-cause rehospitalisation, which will be affected by a survivorship bias in the observed associations, as sepsis survivors are likely to be healthier than patients who die during the sepsis-related hospitalisation and b bias from competing risk as sepsis survivors also have a long-term risk of mortality. Shorter follow-up times in rehospitalisation studies preclude observation of outcome of interest (i.e., censored outcomes). A = Sepsis cohort starting from their index admission which may have greater risk of survivorship bias; B = Ideal cohort to address the research question; and C = Re-hospitalised survivor cohort all patients have the outcome of interest and there is limited understanding of the competing risk issue. Studies with non-sepsis controls provide an estimate the excess risk of rehospitalisation that is unique to sepsis [10, 87]

Fig. 2

Flow diagram showing literature search and results. Flow of information through the different phases of our systematic review recorded PRISMA reporting guidelines. We identified 5184 records from searching MEDLINE, 3810 records from searching EMBASE, 474 records from searching Ovid other/ non-indexed database, and 2039 records from searching the Cochrane library. We identified a further 1037 records from searching the Web of Science database (using TOPIC (septic*) and TOPIC (readmission*) = 244; TOPIC (sepsis*) and TOPIC (readmission*) = 793). This literature search resulted in a total of 12,544 records for our systematic review. ¹At screening stage, we included original articles, review articles, and editorials. ²Reference list from editorial and review articles that met the screening criteria were included for full-text review. ³One full manuscript from reference list scan of the 36 included full manuscripts. ⁴Excluded studies are listed in ESM

Fig. 3

Rate and timing of rehospitalisation. Random effect meta-analysis of proportions by rehospitalisation interval reported in all studies