Dr Samantha Blackley, Dr Amy Todd, Dr Jennifer K Harrison, Prof David J Stott, Prof E Wesley Ely, Dr Zoë Tieges, Prof Alasdair MJ MacLullich and Dr Susan D Shenkin
Background Studies suggest reduced level of arousal (LoA) predicts mortality but study populations and definitions are heterogenous Delirium, in which at least 30% of patients show reduced LoA, is associated with increased mortality Patients with hypoactive delirium may be excluded from studies so studies of delirium and mortality are challenging to interpret Is reduced level of arousal on admission to hospital with acute medical conditions associated with increased mortality in adult patients?
Inclusion Criteria Adults with acute medical illnesses Patients in emergency departments, acute medical/ receiving/ geriatric units, medical assessment units or equivalent Patients in whom an assessment of LoA was made using either a validated scale or a subjective description In-hospital mortality data comparing a drowsy group with a non-drowsy or less drowsy group
Exclusion Criteria Studies including children or excluding patients aged over 65 Studies solely based in ICU, or including patients with surgical conditions Studies solely with patients who had direct CNS injuries: trauma, stroke, brain abscess, brain tumour, meningitis and encephalitis Patients with poisoning, post drowning, post cardiac arrest, with epilepsy or tropical diseases If studies had a mixed population where <50% had excluded conditions, these studies were included to reflect the case mix seen in general medical wards
Avoiding Bias Registered protocol: PROSPERO CRD42016022048 Database bias Searched Medline and Embase References from review articles Forward citation Experts form European Delirium Association and American Delirium Society opinion Publication bias Searched for unpublished data English language bias Non-expert translation where possible
Search terms (Pubmed) 1. consciousness disorders/ 2. drows*.ti,ab. 3. glasgow coma scale/ 4. GCS.ti,ab. 5. glasgow coma scale.ti,ab. 6. AVPU.ti,ab. 7. conscious*.ti,ab. 8. level adj2 arousal.ti,ab. 9. RASS.ti,ab. 10. Richmond adj3 Scale.ti,ab. 11. OSLA.ti,ab. 12. 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 13. mortality/ or hospital mortality/ 14. mortalit*ti,ab. 15. prognosis.ti,ab. 16. 13 or 14 or 15 17. 12 and 16
Data Collection condition studied age range setting sample size prevalence of drowsiness arousal scale used to evaluate drowsiness definition and descriptive terms used to describe LoA in-hospital mortality any adjustments made to the analysis
Author Definition of reduced LoA Aslaner RASS -4/-5 v - 3to-1 v 0-+4 Condition Univariate OR Multivariate OR Unselected 3.46 Nil NA Covariates Rathour GCS 9 Sepsis 5.57 6.02 Age, comorbidities, obs Navinan Mean GCS Unselected Nil 13.1 v 14.8 Nil NA Francia Mean GCS Unselected Nil 13 v 14 0.883 Age, obs Burch A VPU Unselected Nil 5.1 Obs Duckitt A VPU Unselected Nil 3.50 Obs Nicolini Kelly Mathay Scale Otieno GCS 13-15, 9-12, 3-8 COPD Nil 3 v 2 Nil Sex, age, NIV, comorbidities, ABG DKA 39 Nil NA Dutta Mean GCS Myxoedema 19.25 Nil NA Delahaye GCS 8 Endocarditis Nil 4.09 Sex, age, comorbidities, ECHO Calle Prospective cohorts Descriptive CAP 3.81 3.197 Sex, age, Barthel, effusion
Author Definition of reduced LoA Condition Univariate OR Multivariate OR Barfod GCS 13 Unselected 9.29 (9-13) 3.72, (<8) 10.97 Covariates Age, obs Myint Low GCS Unselected 0.877 0.924 Sex, age, obs Sakamoto Japan Coma Scale COPD 2.74 Dull 1.59 Somnolent 1.71 Comatose 4.32 Kaya GCS <15 GI Bleed 11.26 Nil NA Hasegawa Yamuchi Japan Coma Scale Japan Coma Scale Churg Strauss Asthma/ COPD Age, sex, BMI, dyspnoea, ventilation, comorbidities 8.62 3.94 Sex, age, comorbidities nil 3.1 Sex, age, BMI, Barthel, steroids, comorbidities Chih-Hsun Mean GCS HHS nil 14.012 Sex, age, smoking, biochem Conte GCS, EVM CAP 3.99 2.3 Age, comorbidities, obs, creatinine Onadeko Descriptive COPD 6.67 Nil NA Zweig Retrospective cohorts Descriptive Pneumonia 6.62 11.3 Obs, comorbidities
Risk of Bias Assessment RoBANs the selection of participants confounding variables measurement of intervention (exposure) blinding of outcome assessment incomplete outcome data selective outcome reporting
Satistical analysis RevMan Dichotomous data Random effects model I 2 Pooled odds ratio with 95% CI Funnel plots
Results Overall OR of 5.71 [95% CI 4.21-7.74] for the association between reduced LoA and mortality Low quality evidence: high risk of bias, clinical heterogeneity and possible publication bias Studies not included showed similar OR (OR 5.10 95%CI 3.10-8.39, OR 5.65 95%CI 3.35-9.53) Comparable to lactate of 4 on admission (OR for mortality 4)
Continued... This was a heterogenous group of studies covering a wide range of medical conditions Mean age range was 33.4 to 83.8 years Studies considered a variety of medical conditions All were cohort studies; eleven prospective and ten retrospective Different methods of evaluating LoA and cut values of comparison e.g. GCS could have been mean, 13, 9, 8 The prevalence of reduced LoA ranged between 3% to 77% Mortality rates were 1.7% to 58%
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