Out-of-Hours Discharge from intensive care, in-hospital mortality and intensive care readmission rates: a systematic review and meta-analysis

Vollam S. Intensive Care Medicine 2018; 44 (7): 1115-1129. doi: 10.1007/s00134-018-5245-2

Clinical Question

• In patients discharged from a general ICU, is discharge “out-of-hours” compared to discharge “in-hours” associated with subsequent in-hospital mortality?

Background

• Patients discharged from ICU remain at significant risk of in-hospital death, with mortalities reported between 4 – 13% in studies
• Discharges from ICU occasionally occur “out of hours”, when staff and facilities have reduced availability; this is sometimes due to bed pressures
• There are concerns that “out of hours” discharge leads to worse care and thus increased mortality; conversely, patients considered fit for “out of hours” discharge may actually be low risk and therefore have a reduced hospital mortality
• Previous research on the topic has been conflicting- the most recent analysis was conducted by ANZICS and suggested that when severity of illness was corrected for, “out of hours” discharge had no effect on mortality

Design

• Systematic review and meta-analysis
• Registered with PROSPERO, followed PRISMA and MOOSE guidelines where applicable
• 2 authors performed searches in Medline, Embase, Cumulative Index of Nursing and Allied Health Literature, Cochrane Library, and Opengray
• Additional keyword and citation searches from identified studies using Medline and Web of Knowledge
• 2 searches performed- general search for all factors associated with post ICU mortality or readmission, and a specific search on out of hours discharges
• Data summarised using a random effects meta-analysis
• Between study variance computed using DerSimonian and Laird method
• Study quality and risk of bias assessed using Newcastle-Ottawa scale
• Pre-specified sensitivity analyses by omitting studies of different quality/risk of bias
• Disagreements between two reviewers resolved by discussion or referral to a third party
• Publication bias assessed by visual inspection of funnel plot and Egger’s regression
• Heterogeneity of studies assessed using chi-squared test and I-squared statistic

Trials Included

• Search up to and including 12 June 2017
• 1961 papers identified
  • 329 reviewed at abstract
  • 18 studies (14 papers, 4 conference abstracts) passed final screening for mortality analysis with 1,191,178 patients included
    • 9 single centre and 9 multi-centre
    • Study size range: 296 to 263,082 patients
    • Study duration range: 5 months to 9 years
    • ICU admission periods spanned 1994-2014
  • 11 studies passed final screening for readmission analysis with 1,156,904 patients included

Population

• Inclusion criteria for studies:
  • Report in-hospital and/or ICU readmission rates for all patients >=16 years discharged alive from a general, surgical or mixed ICU to a lower level of in-hospital care
  • Report these outcomes separately for patients discharged out-of-hours and in-hours
  • Follow patients to hospital discharge
  • Prospective or retrospective
  • All publication languages with no date restrictions
• Exclusion:
  • Specialist intensive care populations (cardiac, neuro, liver)
  • Studies that separated weekday from weekend, but did not separate in hours from out of hours
  • Data duplicated in larger study
• Only 2/18 trials fully reported baseline characteristics

Comparator

• Discharge “out-of-hours”
  • Variable definition, starting between 1600-2200 and ending between 0559 and 0900

Control

• Discharge “in-hours”

Outcome

• Primary outcome: Significant association between out-of-hours discharge and In-hospital mortality
  • Pooled relative risk estimate 1.39 (95% CI 1.24-1.57; p<0.0001)
  • Adjusted odds ratio (8 studies): 1.33 (95% CI 1.30-1.36; p=0.073)
  • Out-of-hours discharge was associated with significant increases in mortaliy for all definitions of out-of-hours
  • Overall heterogeneity was high (I-squared 90.1%), mainly arising from differences in study size
• Secondary outcomes:
  • Significant association between out-of-hours discharge and ICU readmission (11 studies)
    • Pooled relative risk estimate 1.30 (95% CI 1.19-1.42, p<0.0001)
  • 5 out of 7 studies found significantly higher severity of illness at admission in the out-of-hours groups
  • 2 out of 8 studies found patients discharged at night were significantly younger
• Post-hoc analysis: sub-group analysis based on geographical areas (UK, Europe, Australasia, Americas, Asia)
  • Effect of out-of-hours discharge on mortality remained for studies based in UK, Europe, Australiasia, North and South America. No significant difference found in single small study based in Asia
  • Effect of out-of-hours discharge on readmission:
    • Remained for studies based in
      • Australasia RR 1.18 (95% CI 1.09-1.28)
      • Europe RR 3.02 (95% CI 2.41-3.79)
      • Americas RR 1.14 (95% CI 1.07-1.21)
    • Borderline for studies based in
      • UK RR 1.42 (95% CI 1.00-2.02)

Authors’ Conclusions

• Out-of-hours discharge from ICU is associated with substantial increase in subsequent in-hospital mortality and ICU readmission

Strengths

• Important clinical question with a patient centred outcome
• Predefined, registered and published study protocol
• Multiple techniques used to minimise heterogeneity
• Large patient dataset, multi-national

Weaknesses

• All the studies included, bar one are retrospective cohort studies- they can only demonstrate association, not causation
• Significant heterogeneity between trials demonstrated by an I-squared statistic of 0.9
  • Heterogeneity seen in study size, correction for confounders, and definition of out of hours
• 9/18 of the trials were single centre -further reducing external validity
• A different scoring system was used to assess trials than had been planned in the protocol
• Absence of data in many of included studies, combined with different measures of illness severity used, prevented post-hoc analysis to investigate whether differences between in-hours and out-of-hours populations accounted for differences in outcome.

The Bottom Line

• This meta-analysis of a heterogeneous set of mostly retrospective trials, showed a significant association between “out-of-hours” discharge from ICU and mortality. ICU re-admission was also significantly associated with out-of-hours discharge
• Decisions made to discharge patients “out of hours” will continue to occur, especially in environments where ICU capacity does not match demand
• Hospital systems should be examined to try and minimize discharges out-of-hours

External Links

• [article] Out-of-hours discharge from intensive care, in-hospital mortality and intensive care readmission rates: a systematic review and meta-analysis
• [further reading] Core Standards for Intensive Care Units
• [further reading] Study protocol

Metadata

Summary author: Segun Olusanya
Summary date: 15th September 2018
Peer-review editor: Dave Slessor