WSO - March 2023 - 283

Fleischmann et al.
283
period and was furthermore representative regarding age
and stroke severity. Our findings enhance the class of evidence
that modifiable and non-modifiable risk factors for
delirium of other causes also apply for PSD incidence,
including age, male gender, and treatment-related factors
such as pain, medical devices, and infection. We furthermore
yielded novel evidence that most risk factors also
affect PSD duration. Exploratory imaging analyses revealed
that insular and basal ganglia lesions may increase the risk
for PSD. In a multivariable analysis, PSD and PSI independently
predicted worse outcome at discharge.
Comparison of identified risk factors with
previous studies and practical implications
Non-modifiable risk factors were similar to what would be
expected in general delirium, that is, the risk increases in
males and older patients.13 Previous studies with state-ofthe-art
diagnostic approaches to PSD found that older age
but not gender was a significant risk factor. Yet, a study that
investigated a multicomponent delirium prevention intervention
following stroke also found that males were more
often affected, which confirms our finding.14 A previous
study furthermore identified lower education was a univariable
risk factor in PSD, yet neither the previous nor our
study confirmed this in the multivariable analysis.15 In our
sample, this redundancy of the predictor was explained by
the significant correlation of age and lower education.
None of the previous studies investigated the influence
of treatment-related patterns including pain and presence of
medical devices on the occurrence of PSD. This is somewhat
surprising, since ICU delirium is known to be critically
affected by pain and noxious stimuli induced by the
application of medical devices including urinary catheter
and intravenous lines.16 Our study confirmed that these are
also relevant for PSD. Hence, medical devices should not
be used longer than necessary, and patients should be carefully
assessed for pain.
Substance use neither influenced the incidence nor the
duration of PSD. Previous studies often excluded patients
with known alcohol misuse leaving only a few studies that
investigated
the
influence
of alcohol
on PSD (see
Supplemental Table 1) and only one study reported that the
combination of prior drug and/or alcohol misuse increased
the odds for PSD about 2.5-fold.17 It remains elusive how
much of this effect was due to alcohol, which renders comparisons
with our data difficult, but alcohol (withdrawal)
certainly is an acknowledged risk factor for any type of
delirium.
Implications of neuroimaging for research
and practice
Every patient with presumed ischemic stroke is assessed
with neuroimaging rendering it readily available to assess
the risk for PSD.18 Exploratory analyses revealed that larger
lesion volume and insular or basal ganglia lesion locations
might increase the risk for PSD. Clinical utility of these
findings needs to be prospectively validated, importantly
since CT is often used instead of MRI.
Interaction of PSD and PSI
It is well-established that PSD and PSI are associated with
inferior outcome following ischemic stroke.18,19 We found
that PSD and PSI furthermore independently predict inferior
outcome at discharge after correction for stroke severity
on admission, which deserves close attention. While
delirium and infection are known to interact, importantly
one being a risk factor for the other, their individual or
mutual impact on restitution following stroke remains to be
elucidated, and thus both entities should be closely monitored,
and potentially adjusted for, in interventional clinical
trials that aim to improve neurological outcome by influencing
either PSI or PSD.
Limitations
The investigation of risk factors was not the primary endpoint
of this study, and hence, it was not powered to test
these as dedicated primary hypothesis. Nonetheless, all
evaluated risk factors were pre-defined secondary endpoints
in the study registration, and there were no post hoc
revisions of secondary endpoints, which should minimize
the error. While we may have missed risk factors with effect
sizes lower than Cohen's d of 0.48 (sensitivity based on an
alpha of 0.05 and power of 0.80), we yielded modifiable
risk factors that are in line with risk factors in ICU delirium
and single PSD studies. Another concern might be that our
definition of PSI was not pre-specified. Consequently,
some PSD cases may have been caused by minor infections
rendering the independent contribution of PSD and PSI on
inferior outcome lower than found in this study.20 While we
believe that this effect should be minor, PSI needs to be
more meticulously defined in future studies. Furthermore,
the severity of systemic inflammatory response (SIRS) may
impact on PSD with or without overt infection,20 and should
thus be monitored using established scores, for example,
the National Early Warning Score.
Conclusion
We confirmed that non-modifiable and modifiable risk factor
established for delirium in patients not affected by
stroke also hold true for PSD. The identification of modifiable
risk factors-importantly pain and presence of medical
devices-has immediate practical implications and
should be included in the clinical management of stroke
patients. Particular neuroimaging findings might increase
the awareness for an episode of PSD. In future studies, PSD
International Journal of Stroke, 18(3)
WSO - March 2023

Table of Contents for the Digital Edition of WSO - March 2023
