Identifying Clinical and Acute Psychological Risk Factors For PTSD After Critical Care A Systematic Review

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REVIEW
Identifying clinical and acute psychological risk factors

for PTSD after critical care: a systematic review
D. WADE 1, R. HARDY 2,D. HOWELL 1, M. MYTHEN 3
1The Critical Care Unit, University College London Hospitals NHS Foundation Trust (UCLH), London, UK; 2MRC
Unit for Lifelong Health and Ageing, Division of Population Health, University College London (UCL), UK; 3National
Institute for Health Research Biomedical Research Centre, UCL, London, UK
ABSTRACT
Background. Patients may suffer extreme psychological reactions in intensive care units (ICU), and post-traumatic
stress disorder (PTSD) after leaving hospital. Previous systematic reviews of studies up to 2007 found that the true
prevalence of and consistent risk factors for PTSD after ICU were not established, due to methodological shortcom-
ings of studies. Therefore we aimed to conduct a systematic review of observational studies of post-ICU PTSD from
2008-2012, and to compare them to 1997-2007 studies, with regard to quality, prevalence estimates and risk factors.
Methods. We used a pre-specified protocol, and systematic, explicit methods to identify, select and critically ap-
praise studies. Studies in general ICU settings with mixed-diagnosis patients (N.>30) were included. Risk of bias was
assessed, with lower-risk studies given greater weight. No quantitative synthesis was possible due to heterogeneity,
therefore ranges of estimates and frequencies of risk factors were examined.
Results. The review included 26 papers, 13 from 1997-2007 and 13 from 2008-2012. There were more high qual-
ity studies in the latter period. The range of prevalence estimates from high-quality studies was similar; 8% to 27%
(1997-2007) and 9% to 27% (2008-2012). Clinical risk factors consistently identified over the two periods were
use of benzodiazepines, duration of sedation and mechanical ventilation. Psychological risk factors include stress and
fear experienced acutely in ICU, and frightening memories of the admission.
Conclusion. The quality and number of post-ICU PTSD studies has increased over time, and we can be more
confident in the accumulated findings. Evidence from both periods suggests that up to 27% of ICU survivors suffer
from PTSD. There is also increasing evidence that use of benzodiazepines and duration of sedation, along with fear,
stress and delirium in the ICU are likely risk factors for subsequent PTSD. (Minerva Anestesiol 2013;79:944-63)
Key words: Critical care - Stress disorders, traumatic - Risk factors.
A s critical care medicine advances and more

patients survive, attention has turned to the
quality of their survival. It is now recognised that
is characterised by three clusters of symptoms:
re-experiencing, avoidance and hyper-arousal,
that persist for more than a month and cause dis-
physical and psychological recovery of critical tress or impaired functioning. As well as mental
or other proprietary information of the Publisher.
care patients may be poor.1 Since the late 1990s suffering, patients with PTSD are more likely to
there has been particular concern about the prev- endure worse physical health, quality of life and
alence of post-traumatic stress disorder (PTSD) mortality.5
after intensive care.2, 3 PTSD is an “anxiety disor- Critically ill patients are at high risk of PTSD
der that often follows exposure to an extreme stressor for a number of reasons. They suffer life-threat-
that causes injury, threatens life or physical integ- ening illness, a known traumatic stressor that
rity”.4 The person’s immediate response involves may precede PTSD.4 They undergo treatments
intense fear, helplessness or horror. The disorder and procedures that may save lives, but can also
944 MINERVA ANESTESIOLOGICA August 2013

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IDENTIFYING CLINICAL AND ACUTE PSYCHOLOGICAL RISK FACTORS FOR PTSD AFTER CRITICAL CARE WADE
be invasive and disturbing, including intubation, (21% vs. 57%) at 12 months, but the study had a
ventilation, catheterisation and haemofiltration. historical control rather than RCT design.
Patients describe the cumulative stress of pain, As yet there are too few intervention studies
thirst, hunger, sleep deprivation, noise and light, to warrant a systematic review. However more
inability to communicate, fear of dying and loss information is needed about important, consist-
of control in the intensive care unit (ICU) as ent risk factors for PTSD so that high-risk pa-
overwhelming.6 Furthermore, many patients re- tients can be monitored and followed-up. Fur-
ceive a cocktail of psychoactive drugs including thermore, it is recognized that for psychological
benzodiazepines, inotropes, anti-psychotics and interventions to be successful, they should be
corticosteroids that have poorly understood ef- designed to target modifiable risk factors.18
fects on the brain and emotions of a critically ill All three systematic reviews to 2007 concluded
patient. Consequently, patients may experience that the studies they reviewed had deficiencies in
anxiety, panic, low mood and delirious symp- design, methodology and reporting, as well as
toms including hallucinations and terrifying de- conflicting results, that limited the conclusions
lusions during their stay in an ICU.7, 8 that could be drawn about either prevalence of,
Three systematic reviews of PTSD after criti- or risk factors for post-ICU PTSD. For example,
cal care appraised studies up to 2007. Prevalence Griffiths et al.10 suggested that more rigorous,
of post-ICU PTSD was reported as being in the larger studies focusing on general ICU patients,
range of 0-64% 9, 10 or as having a median point rather than sub-groups, should be carried out.
prevalence of 22%.11 Two reviews 9, 11 identified They also recommended carrying out longitudi-
potential risk factors for PTSD including delu- nal studies with assessments over multiple time-
sional memories of ICU, use of sedation, psy- points. Other recommendations from the reviews
chiatric history, younger age and female gender. were that studies should examine the effects of
However few risk factors were consistently iden- pre-ICU psychopathology, sedation strategies,
tified across studies. and in-ICU delirium on subsequent PTSD.9, 11
PTSD remains a topic of interest in the criti- In order to assess whether the evidence on
cal care literature, with 63 articles published in post-ICU PTSD had improved in the suggested
2011-2012, and more continuing to appear af- ways since publication of the three systematic re-
ter this review was completed. One 2012 study views, we aimed to carry out a systematic review
found that 39% of patients screened positive for of observational studies published from 2008 to
PTSD at 12 months.12 All were acute respiratory 2012. Second, we aimed to compare the newer
distress syndrome (ARDS) patients, a sub-group studies, with the studies published up to 2007, in
of ICU patients who may have higher than aver- terms of size and methodological quality. Third,
age PTSD rates. As well as PTSD in patients, unlike the previous systematic reviews, which in-
there has been increasing recent research interest cluded studies of sub-groups and very small stud-
in PTSD among relatives and ICU staff. Symp- ies, we aimed to include only studies of general
toms of PTSD have been detected in up to 33% mixed-diagnosis ICU patients and studies with
of family members 13 and 24% of ICU nurses.14 at least 30 patients. Finally, our review aimed to
Since 2007 there have also been a small number detect new evidence about clinical and acute psy-
of trials of ICU interventions to prevent PTSD. chological risk factors for, as well as prevalence of
Patient diaries were pioneered in Scandinavia to PTSD, since 2007. We were aware that increased
fill in memory gaps and help patients come to recognition of psychological stress in the ICU,
terms with their experience.15 A pan-European as well as improvements in ICU therapies might
RCT found that patients receiving a diary in- have reduced the prevalence of PTSD and altered
tervention had a significantly lower incidence of risk factors since 2007. The quality of more recent
PTSD than a control group (5% vs. 13%).16 An- studies might be higher and estimates more accu-
other study investigated the effect of early support rate. Our overall aim was to compare 2008-2012
by psychologists in critical care.17 The interven- studies with 1997-2007 studies, with regard to
tion group had a significantly lower risk of PTSD PTSD prevalence, risk factors and quality.
Vol. 79 - No. 8 MINERVA ANESTESIOLOGICA 945

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WADE IDENTIFYING CLINICAL AND ACUTE PSYCHOLOGICAL RISK FACTORS FOR PTSD AFTER CRITICAL CARE
Review questions Types of outcome measures

1. What percentage of survivors of general Studies were selected if they used reliable, val-
intensive care treatment suffers from post-ICU idated questionnaires or interviews for PTSD.
PTSD in the months after intensive care? Studies that used single item measures or un-
2. What are the clinical and acute psychologi- validated bespoke questionnaires for PTSD were
cal risk factors for post-ICU PTSD? excluded.
3. Has the quality of evidence regarding the
first two questions improved between the 1997- Exclusion criteria:
2007 period and the 2008-2012 period?
Studies were excluded if:
Materials and methods 1. their sample size was smaller than 30 par-
ticipants;
The systematic review was conducted ac- 2. they were published only as conference pa-
cording to PRISMA recommendations;19 It was pers or abstracts;
based on a pre-specified protocol, and used sys- 3. full text was not available in English;
tematic and explicit methods to identify, select 4. they were published pre-1997;
and critically appraise studies. The risk of bias in 5. they were set in neo-natal or pediatric
studies was assessed and higher quality studies ICUs.
were given greater weight.
Search strategy
Criteria for study selection
Studies were identified on June 28, 2012 from
Three criteria were used to select studies for the following databases:
inclusion in the systematic review. —— Medline (Ovid SP 1946 -present)
—— Embase (Ovid SP, 1947-present)
Type of studies —— PsycINFO (Ovid SP, 1806 -present)
—— CinahlPlus (EBSCO Host, 1937-present)
Prospective cohort studies, retrospective co- The initial search was carried out on Medline
hort studies, and cross-sectional surveys were using the strategy outlined in Table I. Similar
included in the review. Data from the control searches were carried out on the other three da-
groups in RCTs of interventions to reduce psy- tabases. On September 12, 2012 the searches
chological morbidity in ICU patients were also were re-run. There were nine new references in
considered eligible. the Medline search and none in the others. Only
one new study20 was eligible and has been added
Types of participants to the review. A further study was identified in
October 2012.6
The study populations were adult, mixed-di-
agnosis ICU patients who received intensive care Assessment of risk of bias (quality assessment)
>24 hours in general, medical or surgical ICUs.
Studies of ICU sub-groups such as patients with It should be noted that the PRISMA state-
ARDS or pancreatitis were not eligible as they ment 19 recommends that reviewers should use
are not representative of general ICU patients. the phrase “assessment of risk of bias”, rather
However studies of ICU patients receiving me- than “quality assessment”. The terms are used
chanical ventilation were included. Patients interchangeably in this review. We based our
who receive mechanical ventilation have many quality assessment on methodology checklists 21
different underlying conditions so they are ap- for study designs including cohort studies. Qual-
proximately representative of the general ICU ity criteria for robustness of outcome data were
population. used. For example a study that used the Impact

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Table I.—Medline search strategy.

1. MEDLINE
Search terms
1946-Present
#1 Exp critical care/
#2 (critical care or intensive care or critical illness or ICU or ITU).ti, ab.
#3 1 or 2
#4 (neonatal or pediatric or baby or babies or infant or PICU or child).ti, ab.
#5 3 not 4
#6 Limit 5 to (english language and yr= “1997-Current” and (clinical trial or comparative study or journal article or
multicenter study or randomized controlled trial))
#7 Stress disorders, traumatic/ or stress disorders, post-traumatic/ or stress disorders, traumatic, acute/
#8 (PTSD or “posttraumatic stress disorder” or “post-traumatic stress disorder” or “post traumatic stress disorder” or
“posttraumatic stress” or “post-traumatic stress” or “post traumatic stress”).ti, ab.
#9 7 or 8
#10 6 and 9
Table II.—Quality criteria used in assessment of risk of bias.

The sample
1. A clear definition of source population and clear eligibility criteria for selection of subjects are used, to ensure the sample is
representative.
2. Comparison is made between full participants and those lost to follow up.
3. A power calculation is reported. If not, sample size is small, medium or large.
Outcome
4. The likelihood that some subjects might have the outcome at baseline is accounted for.
5. The outcomes are clearly defined.
6. Evidence is used to demonstrate that measure of outcome is valid and reliable.
7. Follow-up is long enough for outcome to occur.
Risk factors-outcome analysis
8. The study addresses an appropriate and clearly focused question.
9. Any measures of risk factors are reliable.
10. Main potential confounders are identified and taken into account in design and analysis.
11. Confidence intervals have been provided.
12. Appropriate statistical analyses have been carried out.
Overall assessment
How well was study done a) to minimise risk of bias and b) to establish a causal relationship between exposure and effect.?
Adapted from Scottish Intercollegiate Guidelines Network checklist for cohort studies
of Events-Revised Scale 22 scored more highly assigned to each study based on poor (0), ad-
than one using the Impact of Events Scale 23 as equate (1) and good (2) ratings for each of four
the latter includes only two of three symptom selected parameters. These were: Representative-
clusters necessary for a diagnosis of PTSD.4 An- ness of the sample (based on criteria 1 and 2);
other criterion – controlling for confounding Power of the study/sample size (criterion 3), Ro-
factors – is important in evaluating the quality bustness of outcome assessment (criteria 4-7),
of observational studies. A further criterion was and Appropriateness of statistical analysis used
use of appropriate statistical analysis. The quality (criteria 8-12). For sample size, studies with 30-
criteria are shown in Table II. 59 participants were rated poor/small; studies of
Using the recommended system,21 the ma- 60-150 adequate/medium and studies with 150
jority of 1997-2007 studies were assessed as or more participants, or that included a pow-
medium quality, with few poor or high quality er calculation, were good/large. The first three
studies. To provide better differentiation be- parameters applied to prevalence estimation;
tween studies (Table II), numerical scores were the fourth to risk factor-outcome analysis. The

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range of scores was 0-6 out of 6 for prevalence, Synthesis of extracted evidence
and 0-2 out of 2 for the risk factor analysis. This
numerical system was then used to assess the It was not possible to carry out a meta-analysis
2008-2012 studies. of PTSD outcomes due to heterogeneity of both
results and methods of studies, as well as lack of
consistency in reporting results between studies.
Inter-rater reliability Therefore we examined ranges of estimates and
DW carried out quality assessment of 1997- identified reasons for variation in results, using
2007 papers and ER of 2008-2012 papers. Three quality (risk of bias) criteria. Synthesis of infor-
other raters assessed three papers each to assess mation about risk factors was difficult as few
inter-rater reliability. There was 100% agree- studies reported results in a comprehensive man-
ment between all raters in the quality assessment ner, particularly in the pre-2007 period. There-
of the 9 papers. fore we summarised the number of times asso-
ciations were found or not found across studies.
Data extraction strategy
Results
Data were systematically extracted for each
study using a data extraction form by DW and A total of 503 papers were retrieved in the
ER. search outlined above (Figure 1).
Total papers retrieved

N.=503
62 duplicates automatically removed;

102 manually removed
Total without duplicates

N.=339 164 excluded: (Inclusion criteria not
met e.g. neonatal/paediatric settings;
Title screening reviews; PTSD in staff not patients;
qualitative methods; end of life patients;
physiological or mechanistic studies)
Eligible on title
N.=177
128 excluded: (Inclusion criteria not
met e.g. editorials, reviews, sub-groups
Abstract screening
of ICU patients)
Eligible for full paper review

N.=49
Full paper review 23 excluded: (Inclusion criteria not

met: e.g. abstracts only, editorials,
studies of ICU sub-groups, unvalidated
Synthesis PTSD questionnaires used)
N.=26
1997-2007 2008-2012
N.=13 N.=13
Figure 1.—Flowchart of reference retrieval, exclusions and inclusions.

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After removing duplicates, 339 titles and then Exclusion

177 abstracts were screened, and the full-text
versions of 49 potentially eligible papers were In the earlier period, seven studies excluded
reviewed. Of these, 26 papers were eligible for patients for psychiatric or neurological reasons,
inclusion in the review; 13 from 1997-2007 and but from 2008 almost all (11) studies excluded
13 from 2008-2012. those patients (Table III).
Characteristics of included PTSD studies Patient characteristics
There were 13 cohorts of patients in 13 stud- Age

ies in the 1997-2007 period and 12 cohorts in
13 studies from 2008-2012, as two papers 39, 40 There was little difference between the range
covered the same cohort of patients at different of median/mean ages within the two groups of
time-points. There were 2703 unique patients studies; (42-68 years) from 1997 and (48-69
followed up in the 26 studies, and the separate years) from 2008.
totals (1119 in 1997-2007, and 1584 in 2008-
2012) show that more patients were assessed in Sex
the latter period. There were nine medium-size
(N.=60-150) or large (N.>150) studies in the There were larger percentages of men in the
2008 group, compared to seven in the earlier earlier studies (43-76%) compared with the later
group. studies (25-68%).
Both groups of studies took place in homo-
geneous settings (general, medical or surgical Illness severity
ICUs with patients of mixed diagnoses). There
were more multi-site studies published in 2008- Mean or median Apache II scores of cohorts
2012 (5 vs. 3). From 1997-2007 the majority of appeared to be similar; (12-25) in 1997-2007
studies (7) took place in the UK, with five in studies, versus (13-28) in 2008-2012.
mainland Europe and one in the US. Among the
2008-12 studies, seven were in Europe, three in
the UK, two in US and one in Australia. Most of Length of stay in ICU
the earlier studies were prospective cohort stud- There was a shorter range of average stays
ies (8), with one RCT and four other designs. (2.5-21 days) in the 2008 - 2012 studies, com-
By the later period, there were more RCTs (4), pared to a range of 5-52 days in the earlier pe-
fewer prospective cohorts (5) and four others. riod (Table III).
Further details can be seen in Table III.
Quality assessment of PTSD studies

Inclusion/exclusion criteria of included studies
According to our quality criteria, more recent
Inclusion studies (2008-2012) have a lower risk of bias in
estimating prevalence of PTSD, than older ones
From 1997-2007, most studies (11) had in- (1997-2007). Nine new studies had a prevalence
clusion criteria for length of stay (LoS, ranging rating of four or more (out of 6), whereas only
from >1 to >6 days) or mechanical ventilation four old studies scored four or more, and nine
(MV, ranging from >1 to >3 days). But six of old studies had a high risk of bias (Table IV).
the 2008-2102 studies had no inclusion criteria Ranges of response rates (percentage of recruited
for LoS or MV. In the other seven later studies patients assessed at follow-up) were similar in
inclusion criteria were LoS (>2 to >4 days) and both groups of studies (24% to 88% vs. 35%
MV (>12 to >36 hours). to 91%).

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Table III.—Characteristics of post-ICU PTSD studies.

Exclusion criteria in
N assessed for PTSD
First author and year Type of ICU, country, No. sites Inclusion criteria in study study (psychological,
symptoms neurological)
1997-2007 studies
Capuzzo (2005) 24 63 General ICU, Italy LoS > 3days Psychiatric history
Cuthbertson (2004) 25 78 General ICU, UK
Girard (2007) 26 43 Medical ICU, US MV Neurologic disease,

mental disability
Griffiths (2006) 27 108 General ICU, UK LoS>3 days, seen at
followup clinic
Jones (2001) 28 30 General ICU, UK LoS>24h MV Psychotic illness,
Suicide attempt, head
injury
Jones (2003) 29 44 in control General ICUs, UK, 3 sites LoS>48h MV Psychotic illness,
group at 6 m neurosurgery
Jones (2007) 30 238 General ICUs, Europe, 5 sites ICU>48h MV Psychosis,
suicide
Nickel (2004) 31 41 Medical ICU, Germany LoS>24h
Rattray (2005) 32 60 at 6 m 80 at12 m General ICU, UK, LoS>24h, emergencies

Richter (2006) 33 37 Surgical ICU, Germany LoS > 30 days
Samuelson (2007) 7 226 General ICUs, Sweden, 2 sites MV>24h Psychosis, suicide, head
injury, mental disability
Scragg (2001) 34 80 General ICU, UK Head injury, other
injury
Sukantarat (2007) 35 51 at 3 m General ICU, UK LoS>72h
45 at 9 m
2008-2012 studies
Garrouste-Orgeas (2012) 20 36 (two control Medical- surgical ICU, France LoS ≥4 days Dementia
groups, pre-
and post-)
Granja (2008) 36 299 General ICU, Portugal 9 sites LoS >48h
Jackson (2010)37 32 at 3 m 25 at 12 m Medical ICU, USA MV>12h Neurologic deficits,

(control group) neurosurgery
Jones (2010)16 160 (control group) Europe, 6 sites LoS>72h, MV>24h Psychotic illness or
PTSD. confusion
Myhren (2009)38 255 General ICU, Norway LoS>24h Psychiatric history,
severe head injury
Myhren (2010)39 194 General ICU, Norway LoS>24h As above
Rattray (2010) 40 42 UK, 6 sites Head injury,
neurosurgery
Treggiari (2009) 41 129 Medical and surgical ICUs, MV>12h Neurologic conditions,
Switzerland mental disability
Twigg (2008) 42 44 General ICUs, UK, 2 sites Dementia, confusion,
overdose
Van der Schaaf (2009) 43 238 Mixed ICU, Netherlands LoS>48h
Wade (2012) 6 100 General ICU, UK Dementia, persistent

confusion in ICU
Wallen (2008) 44 100 ICU, Australia
Weinert (2008) 45 149 at 2 m 80 at 6 m Medical/surgical ICUs, US MV>36h Psychosis, cognitive

impairment
ICU: Intensive Care Unit; LoS: length of stay; MV=mechanical ventilation; h=hours; IQR: interquartile range; RCT: randomised controlled trial;
SD: standard deviation; SAPS: Simplified Acute Physiology Score. If cells are empty, data were not reported in studies. Some studies reported char-
acteristics of the sample at baseline; others reported characteristics of the sample at follow-up.

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Length of stay in ICU

Design of study Age (years) Sex (% men) Apache II score (or similar)
(days)
Prospective cohort 69 (median) 60% 5 (median) 14 (median)

Prospective cohort 58 (median) 56 % 6 (median) 18 (median)
18-87 (range) 1-51 (range) 4-38 (range)
Prospective cohort 52 (median) 47% 10 (median) 25 (median)
39-65 (IQR) 5-13 (IQR) 20-31 (IQR)
Cross-sectional 57 (mean) 66% 12 (median)
17-85 (range) 2-101 (range)
Case-series prospective 57 (median) 44 % 8 (median) 17 (median)
cohort 17-82 (range) 1-60 (range) 4-28 (range)
RCT (control group) 59 (mean) 57% 13 (mean) 16 (mean)

16 (SD) 18 (SD) 5 (SD)
Prospective cohort 61 (median) 7 (median) 16 (median)
17-86 (range) 2-76 (range) 3-36 (range)
Cross- sectional 47 (mean) 68% 12 (mean, maximum score
obtained)
11 (SD)
Prospective cohort
Retrospective cohort 42 (mean) 76% 52 (mean) 20 (mean)
17 (SD) 20 (SD) 7 (SD)
Prospective cohort 63 (mean) 52% 6 (mean) 18 (median)
13 (SD) 6 (SD) 12 (IQR)
Retrospective cohort 57 (median) 47%
19-90 (range)
Prospective cohort 57 (mean) 43% 17 (mean) 15 (mean)
14 (SD) 17 (SD) 6 (SD)
Non-randomised trial: Pre- 68 (mean) 14 (SD) 52% Pre 21 (mean) 16 (SD) SAPS II score Pre 44 (mean) 14
Pre-and post- controls post- 62 (mean) 16 (SD) 54% Post 13 (mean) 18 (SD) (SD) Post 40 (mean) 15(SD)
Cross-sectional cohort 59 (mean) 44 -71 (IQR) 58% 8 (median) 5-13 (IQR) SAPS II score 37 (median)
30-46 (IQR)
Nested substudy of 68 (median) IQR (56-76) 45% 28 (median) 21-33 (IQR)
RCT (control group)
RCT (control group) 59 (mean), 16 (SD) 62% 13 (mean) 12 (SD) 19 (mean) 7 (SD)
Cross-sectional cohort 48 (mean) 16 (SD) 63% 12 (mean) 10-14 (CI) SAPS II 37 (mean) 35-39 (CI)
Prospective cohort 48 (mean) 16 (SD) 63% 12 (mean) 10-14 (CI) SAPS II 37 (mean) 35-39 (CI)
Prospective cohort 60 (mean) 17-84 (range) 63.% 7 (median) 0-63 19 (mean) 6-34 (range)
(range)
RCT (both groups, 72.3%
light v deep sedation)
Case series cohort 56 (median) 45% 11(median) 7(median) 16 (median) 14 (median) 2
2 sites sites
Cross-sectional cohort 59 (mean) 17 (SD) 66% 9(mean) 10(SD) 15(mean) 6 (SD)
Prospective cohort 57 (mean) 17(SD) 52% 8 (median) 85 (range) 22 (median) 7 (range)
Prospective cohort 63 (mean) 19 (SD) 68% 57h (median) 62h 13 (median) 2-40(range)
(IQR)
Prospective cohort 54 (mean) 45, 63(IQR) 52%

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Table IV.—Assessment of risk of bias (quality assessment) of post-ICU PTSD studies.

Ratings for risk
Quality scores of bias assessment
1. Prevalence ‡ rating (max=6)

4. Analysis of association
2. Risk factor – outcome

1. Representativeness of
3. Outcome assessment
analysis rating (max=2)

Follow-up
First author and year N assessed for PTSD
rate*
2. Sample size†
sample
1997-2007 studies
Capuzzo (2005) 24 63 75% 1 1 0 n/a 2 n/a
Cuthbertson (2004)25 78 70% 2 1 2 1 5 1
Girard (2007) 26 43 24% 2 0 1 2 3 2
Griffiths (2006) 27 108 67% 1 1 1 n/a 3 n/a
Jones (2001) 28 30 unclear 0 0 1 0 1 0
Jones (2003) 29 44 77% 2 0 1 0 3 0
Controls
Jones (2007) 30 238 78% 1 2 2 2 5 2
Nickel (2004) 31 41 n/a 1 0 2 0 3 0
Rattray (2005) 32 60 at 6 m 55% 2 1 1 n/a 4 n/a
80 at 12 m 73%
Richter (2006) 33 37 n/a 1 0 2 0 3 0
Samuelson (2007) 7 226 72% 2 2 2 2 6 2
Scragg (2001)34 80 n/a 1 1 1 0 3 0
Sukantarat (2007)35 51 at 3 m 100% 1 0 1 0 2 0
45 at 9 m 88%
2008-2012 studies
Garrouste-Orgeas (2012) 20 36 (sum of 2 35% 1 0 1 1 2 1
control groups) 41%
Granja (2008) 36 299 n/a 2 2 1 1 5 1
Jackson (2010) 37 32 (3m) 38% 1 0 1 n/a 2 n/a
25 (12m) 29%
Jones (2010) 38 160 (control group) 91% 2 2 2 n/a 6 n/a
Myhren (2009) 38 255 n/a 1 2 1 1 4 1
Myhren (2010) 39 194 76% 2 2 1 2 5 2
Rattray (2010) 40 42 41% 1 0 0 n/a 1 n/a
Treggiari (2009) 41 129 94% 2 2 1 2 5 2
Twigg (2008) 42 44 79% 1 0 2 n/a 3 n/a
Van der Schaaf (2009) 43 238 n/a 2 2 1 n/a 5 n/a
Wade (2012) 6 100 64% 2 2 2 2 6 2
Wallen (2008) 44 100 88% 1 1 2 2 4 2

Weinert (2008) 45 149 at 2 m 54% 2 1 2 1 5 1
80 at 6 m 29%
NB Risk of bias assessment ratings were calculated according to criteria relevant for this review. They do not reflect the quality of other aspects
of the studies, which may have other primary objectives.
*Follow-up rate: % of those enrolled who completed PTSD follow-up (deaths are included in loss to follow-up). No rate given if study cross-sectional.
†Quality scores: 0 (poor); 1(adequate); 2(good). Sample size scores; 0 (small): 30-59, 1 (medium): 60-150, 2 (large): >150 (or power calculation
done)
‡ Prevalence rating was calculated by adding together quality scores 1-3. Risk factor-outcome analysis rating is simply based on quality score 4.

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Table V.—Prevalence of post-ICU PTSD.
Prevalence rating
(lowest risk =6)
Time
from ICU N assessed for PTSD
First author and year discharge PTSD Results as reported Interpretation of results
measure
to outcome
assessment
(1997-2007 studies, arranged in order of prevalence ratings)

Samuelson 2 m or 226 IES-R 8≥30% on IES-R 8% borderline PTSD 6
(2007) 7 later (95%CI: 4.8, 12)
Jones 3m 238 PTSS-14, PDS 9% 9% diagnosis of PTSD 5
(2007) 30 (95%CI: 5.5, 12.9)
had PTSD using PDS
Cuthbertson 3m 78 DTS 22% >27 on DTS 22% possible PTSD 5
(2004) 25 (95%CI: 12.8, 31.2) 12% likely PTSD
12% > 40 on DTS
(95%CI: 0.8, 19.2)
Rattray 6m 60 IES 27≥35% on IES 27% likely at 6m 4
(2005) 32 12 m 80 (95%CI : 17.7, 36.3) 24% likely at 12m
24≥35% on IES
(95%CI: 15, 33)
Richter 35 m 37 Semi-structured 32% (5/6 criteria) 32% sub-syndromal PTSD 3
(2006) 33 psychiatric (95%CI: 17,47) 19% full diagnosis of PTSD
interview. 19% (6 criteria)
(95%CI: 4, 34)
Scragg Variable: 80 IES 30%> unknown cut-off 30% possible PTSD 3
(2001) 34 3-21 m (95%CI: 20, 40) 16% borderline PTSD
15.6%>30 on IES
(95%CI: 7.7, 23.6)
Nickel Variable: 41 PTSS-10. 17%≥35 on PTSS-10 17% likely PTSD 3
(2004) 31 3-15 m SCID (95%CI: 5.5, 28.5) 10% full diagnosis of PTSD
9.76% with SCID
(95%CI: 0.7,18.9)
Griffiths 3m 108 Trauma 52% “PTSD” 52% possible PTSD 3
(2006) 27 screening (95%CI: 42.6, 61.4) on
checklist TSC
Girard 6m 43 PTSS-10 25≥27% on PTSS-10 25% possible PTSD 3
(2007) 26 (95%CI: 12,37.9) 14% likely PTSD
14≥35% on PTSS-10
(95%CI: 3.6, 24.4)
Jones 6m 44 IES 48>19% on IES 48% some impact 3
(2003) 29 (control group) (95%CI: 33.2, 62.8)
Capuzzo 3m 63 ICU memory 0% on IES subscales 0% PTSD 2
(2005) 24 tool
IES
Sukantarat 3m 51 IES 35>26% on IES 35% possible PTSD 2
(2007) 35 9m (95%CI: 21.1, 48.9) 62% possible PTSD
45 62>26% on IES
(95%CI: 47.8, 76.2)
Jones 2m 30 IES 23>19% on IES 23% some impact 1
(2001) 28 (95%CI: 7.9, 38.1)

(2008-2012 studies, in order of prevalence ratings)
Jones 3m 160 PDS 13% 13% diagnosis PTSD 6
(2010)16 (control group) (95%CI: 7.8, 18.2)
Identified by PDS
Wade 3m 100 PDS 27% 27% likely PTSD 6
(2012)6 (95%CI: 18.3, 36) PDS
severity score >18

©
Table V.—Continues
V.—Prevalence from previousPTSD.
of post-ICU page.
Prevalence rating
(lowest risk =6)
Time
from ICU N assessed for PTSD
First author and year discharge PTSD Results as reported Interpretation of results
measure
to outcome
assessment
Treggiari 4 weeks 129 IES-R for 25% 9-10% 9-10% diagnosis PTSD 5
(2009)41 (whole cohort) of patients PCL (95%CI: 4.1, 13.9) met
for 75% of symptom criteria for a
patients presumptive diagnosis
Granja 6m 299 PTSS-14 18% 18% high risk for PTSD 5

(2008)36 (95%CI: 13.75, 22.25)
with PTSS-14 score>49
Myhren 12 m 194 IES 27% 27% likely PTSD 5

(2010)39 (95%CI: 20.8, 33.2)
with IES score >35
van der Schaaf 12 m 238 IES 18% 18% likely PTSD 5

(2009)43 (95%CI: 13.3, 22.7)
with IES score >35
Weinert 2m 149 PDS 17% 17% diagnosis 5

(2008)45 6m 80 (95%CI: 11, 23) 15% diagnosis
15%
(95%CI: 7.2, 22.8) met
diagnostic criteria
Wallen 1m 100 IES-R 13% 13% likely PTSD 4

(2008)44 (95%CI: 6.4, 19.6)
with IES-R score>33
Myhren 4-6 weeks 255 IES 27% 27% likely PTSD 4

(2009)38 (95%CI: 21.6, 32.4)
with IES score>35
Twigg 3m 44 PDS, 16% six criteria 16% diagnosis PTSD 3

(2008)42 IES, PTSS-14 (95%CI: 5, 27) 27% likely PTSD
27% five criteria PDS
(95%CI: 13.9, 40.1)
Garrouste-Orgeas 12 m 36 IES-R 65% pre-group 65% and 75% of patients 2

(2012)20 (sum of two (95%CI: 50.4, 80.6) with some PTSD symptoms
control groups) ≥22 as cut-off
74% post-group
(95%CI: 60.3, 88.3)
≥22 as cut-off
Jackson 3m 32 PTSS-10 10% >35 10% likely PTSD 2

(2010)37 12 m (control group) (95%CI: -0.4, 20.4) 24% likely PTSD
25 24% >35
(95%CI: 7.6, 40.4)
Rattray 2m 42 IES 36% >35 36% likely PTSD 1

(2010)40 6m 42 (95%CI: 21.5, 50.5) 24% likely PTSD
24% >35
(95%CI: 11.1, 36.9)
PTSD measures used:
DTS: Davidson Trauma Scale;47 IES: Impact of Events Scale;23 IES-R: Impact of Events Scale-revised (IES-R);22 PCL: PTSD Checklist;48 PDS:
Posttraumatic Diagnostic Scale;46 PTSS-10: Post-traumatic Stress Syndrome 10-Questions Inventory;49 PTSS-14: UK Post-traumatic Stress
Syndrome 14-Questions Inventory;42 SCID: Structured Clinical Interview for DSM-IV Axis I Disorders;51 TSQ: Trauma Screening Questionnaire.50

©
Outcome assessment of PTSD studies vs. 3) found that gender was not a risk factor for
PTSD. Age and sex were less likely to be identi-
In the 1997-2007 group of studies, outcomes fied as risk factors for PTSD in the later stud-
were assessed at varying time points from 2 to ies than the earlier ones. Psychiatric history was
35 months after ICU discharge (Table V). From found to be a risk factor in five studies (includ-
2008-2012 outcomes were assessed at between ing one where results were unclear) but not in
1 and 12 months. Several PTSD measures were three. Three studies investigated an association
used in the 26 studies, including self-report between time since discharge from ICU and
questionnaires such as the Posttraumatic Diag- PTSD, and found no effect.
nostic Scale (PDS),46 the Impact of Events Scale The clinical risk factors most consistently de-
(IES),23 the Impact of Events Scale-revised (IES- tected were aspects of sedation and mechanical
R),22 the Davidson Trauma Scale (DTS),47 and ventilation (Table VI). From 1997 to 2007 stud-
the PTSD Checklist (PCL);48 screening instru- ies, lorazepam dose,26 administration of mida-
ments such as the Post-traumatic Stress Syn- zolam 6 and duration of sedation 30 were associ-
drome 10-Questions Inventory (PTSS-10),49 the ated with PTSD in three studies. Another study
UK Post-traumatic Stress Syndrome 14-Ques- found no effect of duration of sedation,33 and
tions Inventory,42 and the Trauma Screening one study found no effect of total midazolam or
Questionnaire (TSQ),50 and a clinical interview total propofol dose.26 From 2008 to 2012 stud-
- the Structured Clinical Interview for DSM-IV ies, days of sedation and use of benzodiazepines
Axis I Disorders (SCID).51 were associated with PTSD in one study.6 Light
vs deep sedation 41 and degree of sedation 45 had
PTSD prevalence estimates (1997-2007) no effect in two other studies. Mechanical ven-
tilation was more frequently identified as a risk
The range of PTSD prevalence estimates factor between 2008-12 than 1997-2007, with
found was 0 to 62% across 13 studies (Table V). small effect sizes. One 2008 study found a non-
If only studies with a lower risk of bias (scoring linear association between wakefulness during
4-6) were included in the assessment (N.=4), the ventilation and PTSD (with lower PTSD in the
range of prevalence rate estimates was narrower, least and most awake).45
at 8% to 27%. Median prevalence of the four Other clinical risk factors were identified in
low-risk studies was 13%. one study each: physical restraint,30 administra-
tion of inotropes/vasopressors; administration of
PTSD prevalence estimates (2008-2012) antipsychotics; Therapeutic Intervention Scoring
System (TISS) score; number of organs support-
The range of PTSD prevalence estimates was ed, days of cardiovascular support and number
9% to 75% across 13 studies. When only stud- of psychoactive drug groups given.6 Diagnostic
ies with lower risk of bias (4-6) were included groupings, illness severity scores such as Apache
(N.=9), the range of estimates was 9% to 27%. II and LoS in the ICU were not identified as risk
Median prevalence of the nine low-risk studies factors for PTSD in either period (Table VI).
was 18%. Acute psychological risk factors were fre-
quently identified as risk factors for PTSD,
Risk factors for PTSD with 28 associations found across both periods
(Table VII). In studies focusing on memory

There were eight studies with a low or me- and delirium, factors measured were traumatic
dium risk of bias (1-2) for risk factor-outcome memories (association found in 1 study),26 pain
analysis in 2008-2012 versus four from 1997- memories (association in 2 studies),38, 39 factual
2007 (Table VI). Pooling data from the two memories (2 associations),38, 39 delusional/de-
periods, Table VII shows that five studies iden- lirious memories (association in 6; no associa-
tified age (usually younger age) as a risk factor, tion in 2), intrusive memories (association in 2
whereas seven studies did not. Most studies (7 studies),6, 36 amnesia in ICU or pre-ICU (asso-

©
ciation in 2 studies,6, 36 none in 1 study),45 and studies using the same measure used different
delirium (association in 1 study;6 no associa- cut-points denoting different meanings (such as
tion in another).26 Mood, stress, fear, agitation, likely PTSD, possible PTSD, probable PTSD,
panic, loss of control and inability to express borderline PTSD and diagnosed PTSD). For ex-
wishes in the ICU, along with pessimism, peri- ample in studies using the IES,23 some used a
traumatic dissociation and illness perceptions cut-point of 19, some of 26 and others of 30 or
were other psychological risk factors tested (in 35. Clearly this would result in different preva-
6 studies). All had positive associations with lence rates being calculated. There was more
PTSD, with the exception of peritraumatic dis- standardisation with regards to cut-points in the
association.20 later studies. For example all 2008-2012 studies
using the IES used a cut-point of >35.
Discussion When studies were arranged in order of time
to follow-up (table not shown) no pattern could
In this systematic review, 13 eligible studies be discerned. Of note, in spite of the recommen-
of post-ICU PTSD were retrieved from 1997- dation of earlier systematic reviews, few longitu-
2007 and 13 studies from 2008-2012. This sug- dinal studies with PTSD assessment at multiple
gests an increasing interest in post-critical care time-points were carried out. Therefore there
PTSD in the last four years. Compared to 1997- is still no clarity about the likely trajectory of
2007, the 2008-12 period included more multi- PTSD in ICU survivors over time. On exami-
site studies, more medium to large studies, less nation, the most important source of variation
restrictive inclusion criteria, more RCTs and a for PTSD results was in the quality of studies.
larger number of patients overall. More of the Therefore, table 5 showing PTSD prevalence
later studies were of high quality (i.e. had a lower and table 6 showing risk factors for PTSD were
risk of bias) than earlier studies. ranked in order of quality scores within the two
There was a remarkable concordance about time periods.
the prevalence of PTSD, based on the higher The likely interpretation of the 2008-2012
quality studies from both periods (Table V). The data (based on a larger number of high quality
range of estimates for PTSD from 1997-2007 studies) is that 9% -15% of ICU survivors would
was 8-27% with 13% as the median prevalence. fulfil all diagnostic criteria for PTSD, while 13%
From 2008-2012 studies, PTSD was estimated to 27% are highly likely to have PTSD or meet
between 9-27% with a median prevalence of most diagnostic criteria. The median prevalence
18%. Variation in results may be related to dif- suggests that around one in five critical care pa-
ferences in ICU populations, different measures tients develop high levels of PTSD symptoms
used with different diagnostic thresholds and after intensive care.
different lengths of follow-up. Interventions to reduce PTSD prevalence
It should be noted that eight out of 26 stud- would clearly be desirable 52 and in the UK,
ies used the (unrevised) IES 23 as a measure of National Institute of Health and Clinical Excel-
PTSD. The IES is a good measure of distress re- lence guidelines recommend that support and
lated to life events but is not a measure of PTSD, rehabilitation be made available to prevent fu-
as it includes only two of the three clusters of ture psychological morbidity.53 However, to de-
PTSD symptoms.4 Others used screening tools sign effective preventative interventions, a clear
that cannot confirm the presence of PTSD, such picture of important risk factors is needed.18
as the PTSS-10 49 or TSQ.50 In the 2008 period, Across the 26 studies, there was evidence for
more studies (four vs one) used the PDS,46 a and against the importance of socio-demograph-
questionnaire that conforms to current diagnos- ic risk factors such as younger age and female
tic criteria for PTSD.4 A further three (vs. one sex, but fewer recent studies found associations
from 1997-2007), used the IES-R,22 which in- with those factors (Table VI). No studies in the
cludes the three clusters of PTSD symptoms. earlier, and very few in the later period, investi-
In the early period, it was problematic that gated the role of ethnicity or socio-economic cir-

©
cumstances in post-ICU PTSD.6, 38, 39 The im- Exactly why sedation factors should be linked
portance of previous psychiatric history remains to longer-term PTSD is not yet obvious. Cer-
uncertain as very few 2008-12 studies tested it as tainly there has long been concern, and indeed
a risk factor, although the earlier systematic re- controversy, about reports that extended periods
views had strongly recommended that it should of benzodiazepine usage in the community, par-
be included in future studies. ticularly among older patients, may be linked to
Similar to 1997-2007 studies, the 2008-2012 poor long-term neuropsychiatric outcomes in-
studies found that clinical factors such as diag- cluding cognitive decline, psychotic symptoms,
nostic group, illness severity scores such as the anxiety and depression.54, 55 These effects have
Apache II and length of stay in the ICU were been attributed to benzodiazepine-associated
not risk factors for PTSD. Of note, one 2012 brain damage,56 or deficiencies in serotonin,
study 6 found associations with both TISS score noradrenaline and dopamine caused by benzo-
and number of organs supported and PTSD. diazepines.54
These variables may be a better reflection of ill- Other studies have found that benzodiazepine
ness severity during an admission than Apache II use in the ICU is associated with a greater like-
scores measured within 24 hours of admission. In lihood of delirium.30, 57 This is possibly due to
fact TISS score is a measure of number and type the effects of these drugs on levels of neurotrans-
of interventions received; it is possible therefore mitters such as dopamine or acetylcholine, par-
that increasing, more invasive interventions rath- ticularly in critically ill patients with deranged
er than illness severity are a risk factor for PTSD. physiology, whose ability to excrete drugs may
Other clinical factors such as sedation and me- also be impaired. It may be that patients suf-
chanical ventilation continued to be investigated fering delirium, especially if hallucinations and
(Table VI), as recommended by earlier reviews. paranoid delusions are among their delirious
Between 1997 and 2012, 7 studies investigated symptoms, are more likely to develop PTSD. But
a link between sedation and PTSD. Between although a number of studies have shown that
1997-2007 3 high-quality studies found posi- patients who have memories of paranoid delu-
tive associations between PTSD and lorazepam sions shortly after leaving the ICU are more likely
dose,26 administration of midazolam,7 and dura- to develop PTSD, an association between acute
tion of sedation and opiates;30 while one low- delirious symptoms and PTSD was only found
quality, small study (N.=37) found no associa- in one of the 26 studies reviewed here.6 Another
tion with duration of sedation.33 One of these likely explanatory mechanism may be that ben-
studies (also small, N.=43) 26 also found no posi- zodiazepines are known to cause amnesia as well
tive association between other sedatives (apart as sedation.58 Patients who have long periods
from lorazepam) and PTSD. From 2008-2012, of amnesia for real events that occurred in the
only one high-quality study found positive as- ICU, while remembering terrifying delusional
sociations with both duration of sedation and memories, may be more prone to develop PTSD.
administration of benzodiazepines, and PTSD.6 While these explanations remain in the realms of
However another high-quality study found no hypothesis, the clinical implications of the stud-
association between depth of sedation (heavy ies that measured sedation as a risk factor, are that
vs light) and PTSD 41 while a medium-quality reducing the use of benzodiazepines and length
study 45 did not find an association with seda- of time a patient is sedated where possible, could
tion intensity score (average sedative exposure reduce their risk of ICU-related PTSD in future.
per hour) and PTSD. Use of mechanical ventilation and duration
Although evidence is not definitive, these re- of MV were found to be risk factors in 3 out
sults suggest that receiving benzodiazepines for of 4 later studies (2008-2012), but no associa-
sedation, or being sedated for longer, are risk fac- tions with days of ventilation were found in 3
tors for PTSD. However the depth of sedation out of 4 earlier studies (1997-2007). It is known
or average amount of sedative drug received in that mechanical ventilation, particularly if pro-
a given time do not appear to increase the risk. longed, can be a highly stressful, invasive and

©
Table VI.—Risk factors for post-ICU PTSD.
Age/other socio- Severity of

1stauthor/year Statistical analysis of risk factors Sex
demographics illness
1997-2007 studies in order of quality rating

Girard 2007 26 Multivariable Age Y Y N
logistic regression (younger people at greater risk) (females at greater risk)
Jones 2007 27 Structural equation modelling
Samuelson 2007 7 Multivariable logistic regression Age Y Y N

younger female
Cuthbertson 2004 25 Univariable Age Y N N

(Spearman’s younger
correlations)
Scragg 2001 34 Multivariable linear regression Age N N
Jones 2001 28 T-test,
ANOVA
Nickel 2004 31 Mann Whitney test N
Richter 2006 33 T-test, Mann Whitney test Age N N
Jones 2003 29 ANOVA
Sukantarat 200735 Univariable (Spearman’s correlations) Age N N

2008-2012 studies in order of quality
Myhren 2010 39 Multivariable logistic regression Age N N N
Education level, low Y
Unemployed Y
Treggiari 2009 41 T-test

Wade 2012 6 Multivariable linear regression Age N N N
Socio-economic N
Ethnicity N
Wallen 2008 44 Multivariable logistic regression Age Y N Y

(younger)
Garrouste-Orgeas, Kruskal-Wallis, Age N Y N
2012 20 chi square female
Granja 2008 36 Multivariable logistic regression Age N N N
Myhren 2009 38 Multivariable linear regression Age Y N N

(4-6 weeks) (older)
Unemployed Y
Weinert 2008 45 T-test, ANOVA, correlations

(2m and 6m)
Y: association found, N: no association found; MV: mechanical ventilation

Risk factor analysis rating: 2= lowest risk of bias. 1= moderate risk of bias 0: highest risk of bias
* Among psychological factors, FMs= factual memories, DMs: delusional/delirious memories, IMs: intrusive memories

©
Prior Psychological/
Clinical/other Diagnosis LoS Risk factor
psychological neuro-cognitive
factors groups in ICU analysis rating
history factors*
Total lorazepam dose Y Days of delirium in ICU N N 2

Midazolam N Measured at 6m: Traumatic memories Y
Propofol N
Days of MV N
Y Prolonged sedation Y Measured at 1-2 weeks: N
Physical restraint Y DMs Y 2
Use of midazolam Y Agitation in ICU Y N 2
Days of MV N Measured at 5 days:
ICU fear Y
ICU stress Y
DMs N
Amnesia N
Y Days MV Y N N 1
Time since discharge N N 0

N Measured at 2 weeks: N
DMs Y 0
Y 0
?unclear
N Duration MV N N N 0
?unclear Duration of sedation N
Time to follow-up N
Measured at 2 weeks: 0
DMs Y
0
Time of outcome Measured at 4-6w: N N 2

assessment N Pessimism Y
Pain memories Y
Lack of control Y
FMs Y
DMs N
Light vs deep sedation N 2
Y Days of sedation Y Measured in ICU: N N 2
Benzodiazepines Y Mood Y
Inotropes/ IM Y
vasopressors Y Illness perception Y
Antipsychotics Y Stress Y
TISS score Y Delirium Y
Number organs Y Amnesia in ICU Y
Days MV Y
Days CV support Y
Number drug groups Y
N N 2
N Receiving Measured at 3m: N N 1

endotracheal MV Y Peritraumatic dissociation N
Measured at 6m: N N 1
DMs Y
Panic Y
IM Y
Amnesia for pre-ICU hospital stay Y
MV received Y Measured at 4-6w: N N 1
Duration of MV N Pessimism Y
Pain memories Y
Lack of control Y
Inability express needs Y
DMs Y
FMs Y
Wakefulness in MV N Measured at 2m: 1
(non-linear; lower PTSD in ICU amnesia N
most and least awake) DMs Y
Degree of sedation N

©
Table VII.—Summary table of post-ICU PTSD risk factors.
position or ethnicity
Other psychological
Psychiatric history
Diagnosis in ICU
Types of memory
Socio-economic
Illness severity
and delirious
Days in ICU
Studies
symptoms
Sedation
factors ‡
MV
Age
Sex
1997-2007 Y (3) Y (2) Y (0) Y (4) Y (0) Y (0) Y (0) Y (3) Y (1) Y (5)* Y (2)
(n=10) N (3) N (2) N (0) N (2) N (4) N (6) N (5) N (2) N (3) N (3) N (0)
2008-2012 Y (2) Y (1) Y (3) Y (1) Y (0) Y (1) Y (0) Y (2) Y (3) Y (12) † Y (9)
(n=8) N (4) N (5) N (2) N (1) N (6) N (5) N (6) N (2) N (1) N (2) N (1)
Total Y (5) Y (3) Y (3) Y (5) Y (0) Y (1) Y (0) Y (5) Y (4) Y (17) Y (11) ‡
N (7) N (7) N (2) N (3) N (10) N (11) N (11) N (4) N (4) N (5) N (1)
Y: significant effect found for factor (x) number of times
N: no significant effect found for factor (x) number of times
*traumatic memories, delirious memories or amnesia
†pain memories, factual memories, delusional memories, intrusive memories, delirium, amnesia in ICU and pre-ICU
‡Stress, agitation, fear, panic, mood, loss of control, inability to express needs in ICU. Also pessimism, peritraumatic dissociation and illness per-
ceptions
terrifying procedure. It is associated with life- Emotional reactions measured in or imme-

threatening illness such as respiratory failure and diately post-ICU were found to predict PTSD
the inability to breathe independently, factors in two high quality studies, one from each time
that would be expected to cause anxiety. There- period.6, 7 In one study acute emotional reac-
fore it would not be unusual if the experience of tions confounded most other risk factors.6 Loss
MV were to trigger an anxiety disorder such as of psychological control and the personality trait
PTSD. Nevertheless in three of the four studies of pessimism were also associated with PTSD in
which detected the association, it was found to two later high quality studies of the same cohort
have a small effect size in a univariable analysis. of patients.38, 39 It is likely that acute psychologi-
This suggests that MV is not a strong risk factor cal or neuro-cognitive factors such as the impact
for PTSD, and its effect may be explained by the of delusions and delirium, and emotional stress
related factor of sedation, as the two clinical fac- in the ICU, are important risk factors for PTSD,
tors tend to occur together. but still more research is needed to confirm these
Judged by the number of associations found findings
across studies,28 psychological reactions to ICU The experience of hallucinations and delu-
would be the most important group of risk fac- sions, along with the threat to life from critical
tors for PTSD. However there are problems illness, and the stressful and invasive procedures
with interpreting these associations. From 1997- it necessitates, is likely to lead to extreme reac-
2007, a number of studies showed that traumat- tions such as anxiety, panic attacks and low mood
ic or delusional memories were associated with in critical care patients. Without psychological
PTSD. These were measured at times between support to deal with these symptoms, the patient
2 weeks and 6 months after ICU, and could may continue to be traumatized after transfer to
therefore be symptoms of disorder (acute stress a medical or surgical ward. As relatives may also
disorder or PTSD) rather than risk factors for suffer from PTSD,13 there may be conflict within
a disorder. The picture is even less clear in the families after ICU, causing further stress during
2008 to 2012 studies, as many types of memory a patient’s recovery period at home. These experi-
(delusional/delirious memories, factual memo- ences may predispose patients to develop mental
ries, pain memories, intrusive memories, ICU health disorders such as PTSD after the ICU.
amnesia, pre-ICU amnesia) were investigated at Strengths of this review are that it was based on
different time points in one or two studies each. a prespecified protocol and used systematic and

©
explicit methods to identify, select and appraise

studies. Assessment of risk of bias (quality assess- Key messages
ment) was carried out. No studies of diagnostic —— Up to 27% of ICU survivors suffer
sub-groups of ICU patients were included, and from PTSD up to a year after leaving the
therefore estimates of prevalence were not in- unit, with likely serious consequences for
flated by patient groups with exceptionally high their health and well-being.
rates. The review included studies of mechani- —— The most important known clinical
cally ventilated ICU patients. As ventilated pa- risk factors for post-ICU PTSD are use of
tients have many underlying conditions, they are benzodiazepines and duration of sedation in
broadly representative of the ICU population. the ICU.
A limitation of the review was that no statisti- —— Extreme stress reactions, delirious
cal aggregation of results was possible due to het- symptoms and memory problems in the
erogeneity of methods and results. Therefore we ICU are risk factors for PTSD, but have not
have presented medians and ranges of estimates been investigated in a consistent way.
of PTSD. We could not carry out a meta-anal- —— The quality and quantity of evidence
ysis, and therefore could not test quantitatively about prevalence of and risk factors for post-
for publication bias, which is a common limita- ICU PTSD have improved over time, but
tion of systematic reviews. We did not include cannot yet be considered definitive.
unpublished results or results published only in
abstracts or conference papers. This review also
carries the risk of bias due to possible selective re-
porting of associations within studies. It is likely References
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Acknowledgments.—We are very grateful for the contribution of Elijah Rhone (ER), who carried out data extraction of the 2008-12 studies,
and Kate Cheney the UCL librarian who advised on the search strategy. We would also like to thank Rosalind Raine and John Weinman
for their support in supervising the early stages of work on this systematic review.
Funding.—DW is funded by, and DH and MM receive a portion of their funding from, the UCLH/UCL National Institute of Health
Research Biomedical Research Centre. Rebecca Hardy is supported by the MRC. There are no conflicts of interest.
Received on October 8, 2012 – Accepted for publication on March 25, 2013.
Corresponding author: Dr. D. Wade, Health Psychologist, The Critical Care Unit, UCLH NHS Foundation Trust, 235 Euston Rd, Lon-
don NW1 2BU, UK. E-mail: Dorothy. Wade@uclh.nhs.uk

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Identifying clinical and acute psychological risk factors

A s critical care medicine advances and more

944 MINERVA ANESTESIOLOGICA August 2013

Vol. 79 - No. 8 MINERVA ANESTESIOLOGICA 945

Review questions Types of outcome measures

946 MINERVA ANESTESIOLOGICA August 2013

Table I.—Medline search strategy.

Table II.—Quality criteria used in assessment of risk of bias.

Vol. 79 - No. 8 MINERVA ANESTESIOLOGICA 947

Total papers retrieved

62 duplicates automatically removed;

Total without duplicates

Eligible for full paper review

Full paper review 23 excluded: (Inclusion criteria not

Figure 1.—Flowchart of reference retrieval, exclusions and inclusions.

948 MINERVA ANESTESIOLOGICA August 2013

After removing duplicates, 339 titles and then Exclusion

Characteristics of included PTSD studies Patient characteristics

There were 13 cohorts of patients in 13 stud- Age

Quality assessment of PTSD studies

Vol. 79 - No. 8 MINERVA ANESTESIOLOGICA 949

Table III.—Characteristics of post-ICU PTSD studies.

Girard (2007) 26 43 Medical ICU, US MV Neurologic disease,

Rattray (2005) 32 60 at 6 m 80 at12 m General ICU, UK, LoS>24h, emergencies

Jackson (2010)37 32 at 3 m 25 at 12 m Medical ICU, USA MV>12h Neurologic deficits,

Wade (2012) 6 100 General ICU, UK Dementia, persistent

Weinert (2008) 45 149 at 2 m 80 at 6 m Medical/surgical ICUs, US MV>36h Psychosis, cognitive

950 MINERVA ANESTESIOLOGICA August 2013

Length of stay in ICU

Prospective cohort 69 (median) 60% 5 (median) 14 (median)

RCT (control group) 59 (mean) 57% 13 (mean) 16 (mean)

Prospective cohort 57 (mean) 17(SD) 52% 8 (median) 85 (range) 22 (median) 7 (range)

Vol. 79 - No. 8 MINERVA ANESTESIOLOGICA 951

Table IV.—Assessment of risk of bias (quality assessment) of post-ICU PTSD studies.

1. Prevalence ‡ rating (max=6)

2. Risk factor – outcome

analysis rating (max=2)

Wallen (2008) 44 100 88% 1 1 2 2 4 2

952 MINERVA ANESTESIOLOGICA August 2013

Table V.—Prevalence of post-ICU PTSD.

(1997-2007 studies, arranged in order of prevalence ratings)

(2001) 28 (95%CI: 7.9, 38.1)

Vol. 79 - No. 8 MINERVA ANESTESIOLOGICA 953

Granja 6m 299 PTSS-14 18% 18% high risk for PTSD 5

Myhren 12 m 194 IES 27% 27% likely PTSD 5

van der Schaaf 12 m 238 IES 18% 18% likely PTSD 5

Weinert 2m 149 PDS 17% 17% diagnosis 5

Wallen 1m 100 IES-R 13% 13% likely PTSD 4

Myhren 4-6 weeks 255 IES 27% 27% likely PTSD 4

Twigg 3m 44 PDS, 16% six criteria 16% diagnosis PTSD 3

Garrouste-Orgeas 12 m 36 IES-R 65% pre-group 65% and 75% of patients 2

Jackson 3m 32 PTSS-10 10% >35 10% likely PTSD 2

(95%CI: 7.6, 40.4)

Rattray 2m 42 IES 36% >35 36% likely PTSD 1

954 MINERVA ANESTESIOLOGICA August 2013

(Table VII). In studies focusing on memory

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Vol. 79 - No. 8 MINERVA ANESTESIOLOGICA 957

Table VI.—Risk factors for post-ICU PTSD.

Age/other socio- Severity of

1997-2007 studies in order of quality rating