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ognitive changes after major surgery have received among studies.7,8 Postoperative cognitive dysfunction
group were used to gain information on practice effect and Sample size was calculated to obtain a power of 0.85 at
normal distribution in test results for this age group, and z a significance level of 0.05. We sought to obtain sufficient
scores were calculated. These diagnostic criteria are in line data on early POCD (at 1–2 weeks) to discern a reduction
with the recommendations from the International Study of from the previously reported 20% POCD incidence among
Post-Operative Cognitive Dysfunction (ISPOCD) group.8 the elderly undergoing major surgery (from the ISPOCD
Besides the neuropsychological tests, patients were asked group) to an anticipated level of about 10% which required
to complete a questionnaire preoperatively about their evaluation of 220 patients.
comorbidities, daily use of medication, educational status,
and sleep pattern with the Pittsburg Sleep Questionnaire RESULTS
Index.18 All patients were screened for sleep apnea and We approached 311 patients for participation in the study.
dementia preoperatively with the Berlin Questionnaire Eighty-four patients declined to participate, and 2 patients
and MMSE.19,20 Information about anesthetic technique were excluded due to MMSE score <24. The remaining 225
and duration, procedure duration, use of analgesics, use of patients were included. Five patients (2%) failed to show
hypnotics during hospitalization, postoperative complica- up for their first postoperative evaluation, and 25 failed
tions, and LOS were recorded. Pain at rest and while walk- to show up for their final evaluation at 3 months (drop-
ing were assessed using a numerical ranking scale of 0 to out rate 11.2% for final visit). Hence, the remaining 220
10 (0 = “no pain” and 10 = “the most excruciating pain patients’ cognitive test results were included in the diag-
imaginable”) before each test session. To assess inflamma- nosis of early POCD (at 1–2 weeks) and from 200 patients
tion, CRP blood concentration was analyzed at the preop- at 3 months.
erative test session, on postoperative day 1 or 2 and on the The median age was 68 years (IQR 64–73 years). Eighty-
first postoperative test session (1–2 weeks postoperatively). one patients had TKA and 144 had THA. The median
Data on clinically overt postoperative delirium in this MMSE score was 28 (IQR 24–30), and mean LOS was 2 days
group have been reported previously.16 (IQR 2–3). Spinal anesthesia was performed in 203 patients
(90.2%), and 49.7% of these received supplemental propofol
Statistics sedation. The remaining 22 (9.9%) patients received general
The z scores were calculated as described in detail else- anesthesia. Comorbidity, perioperative data, complications,
where.8 Continuous data are reported in the tables as and readmission are shown in Tables 1 to 3.
median and interquartile range (IQR) and categorical data
as frequency (n) and percentage, stratified by early POCD.
The association between continuously valued variables and Table 1. Comorbidity for Patients Undergoing Hip or
POCD was assessed by the difference in medians of patients Knee Arthroplasty
with or without POCD. The association between categorical Comorbidity No. of patients
variables and POCD was assessed by the difference in risk Hypertension 126
Heart disease (AF, heart failure, valve disease) 28
for POCD between the category and the baseline category
Lung disease (asthma, COPD) 15
in percent points, including the association between early- Diabetes—IDDM/NIDDM 1/17
and late-onset POCD. A 95% confidence interval (CI) and Psychiatric illness 17
corresponding P value were calculated for the above differ- Prior stroke 12
ence estimates with a nonparametric bootstrap using 10,000 Sleep apnea 7
replications, this is also the case for the 95% CI for incidence AF = atrial fibrillation; COPD = chronic obstructive pulmonary disease; IDDM/
estimates.21 NIDDM = insulin/noninsulin-dependent diabetes.
Table 2. Perioperative Data Stratified on the Presence of Early Postoperative Cognitive Dysfunction
Perioperative data Early POCD Not early POCD Differencea P value
ASA class, n (%)
I 6 (8.7) 63 (91.3) 0
II 10 (7.2) 129 (92.8) −1.5 (−9.8 to 6.3) 0.74
III 4 (33.3) 8 (66.7) 24.6 (−2.3 to 56.9) 0.071
IV 0 0 — —
Procedure, n (%)
Hip arthroplasty 11 (7.7) 131 (92.3) 0
Knee arthroplasty 9 (11.5) 69 (88.5) 3.8 (−4.5 to 12.5) 0.40
Duration of anesthesia (min), median (IQR) 120 (95 to 135) 115 (100 to 135) −5 (−25 to 20) 0.44
Duration of surgery (min), median (IQR) 63 (45 to 75) 55 (45 to 70) −8 (−20 to 10) 0.44
Anesthesia method, n (%)
Neuraxial block 18 (9.1) 180 (90.9) 0
General 2 (9.1) 20 (90.9) 0 (−11.1 to 14.9) 0.96
Intraoperative sedation, n (%)
No 9 (7.8) 107 (92.2) 0
Yes 11 (10.6) 93 (89.4) 2.8 (−4.8 to 10.5) 0.47
Length of stay (d), median (IQR) 2.5 (2.0 to 3.0) 2.0 (2.0 to 3.0) −0.5 (−1.0 to 1.0) 0.39
POCD = postoperative cognitive dysfunction; IQR = interquartile range.
a
Difference in risk for early POCD between the corresponding category and the baseline (first) category in percent points and 95% confidence interval (categorical
variables), or difference in medians between early POCD and not early POCD and 95% confidence interval (continuous variables).
Table 4. Data Regarding Inflammation C-Reactive Protein, Sleep Quality (Pittsburg Sleep Questionnaire
Index), Pain, and Opioid Use
Variable Early POCD Not early POCD Differencea P value
CRP at preoperative test (mmol/L) 2.0 (1.0 to 7.5) 2.0 (1.0 to 4.0) 0.0 (−2.5 to 1.0) 0.84
CRP at postoperative day 1 (mmol/L) 54.0 (20.0 to 70.0) 64.0 (46.0 to 80.0) 10.0 (−6.5 to 30.5) 0.38
CRP at postoperative day 2 (mmol/L) 194.5 (77.0 to 280.0) 142.0 (51.0 to 206.0) −52.5 (−148.5 to 63.0) 0.26
CRP at 1st postoperative test (mmol/L) 15.0 (7.0 to 25.0) 15.0 (8.0 to 21.0) 0.0 (−11.0 to 8.0) 0.69
PSQI at preoperative test 6.0 (3.0 to 8.5) 6.0 (3.0 to 9.0) 0.0 (−3.0 to 2.0) 0.55
PSQI at 1st postoperative test 9.5 (3.5 to 11.0) 7.0 (4.0 to 10.0) −2.5 (−4.0 to 3.0) 0.26
Pain score at preoperative test—at rest 2.0 (0.0 to 5.0) 2.0 (0.5 to 3.0) 0.0 (−2.0 to 2.0) 0.99
Pain score at preoperative test—activity 5.0 (3.5 to 8.0) 5.0 (4.0 to 6.5) 0.0 (−2.5 to 1.5) 0.68
Pain score at 1st postoperative test—at rest 2.5 (0.0 to 5.0) 2.0 (0.5 to 3.0) −0.5 (−2.5 to 1.0) 0.55
Pain score at 1st postoperative test—activity 3.5 (1.5 to 5.5) 3.5 (2.0 to 4.5) 0.0 (−2.0 to 2.0) 0.67
Opioid useb in hospital (mg/d) 31.7 (15.0 to 40.0) 22.5 (10.0 to 35.0) −9.2 (−20.0 to 6.7) 0.33
Opioid useb in hospital (mg/d/kg) 0.33 (0.17 to 0.48) 0.29 (0.14 to 0.45) −0.04 (−0.19 to 0.11) 0.48
Median values (interquartile range), stratified on early POCD.
CRP = C-reactive protein; PSQI = Pittsburg Sleep Questionnaire Index; POCD = postoperative cognitive dysfunction.
a
Difference in medians between early POCD and not early POCD and 95% confidence interval.
b
Opioid dosage has been calculated in equipotent morphine dosage where medication other than oral morphine was administered.
risk factors (inflammation, pain, disturbed sleep, opioid postoperative recovery period with decreased function,
use). However, early POCD did not clearly predispose to postoperative pain, and opioid administration, all affect
late-onset POCD. We observed very few postoperative com- elderly patients more than their younger counterparts.
plications, and an analysis of a possible association between The fast-track approach uses a multimodal pain manage-
early- or late-onset POCD with postoperative complications ment regime to reduce the use of opioids and pain levels.
was not meaningful. This study did not analyze pain scores immediately after
Our data suggest a lower incidence of early-onset POCD surgery, but other studies, with the same approach and
than previously reported.22–26 The largest trial to evalu- similar patient group, have reported only moderate pain
ate POCD in noncardiac surgery is still the ISPOCD study during ambulation in the first 48 hours postoperatively,28 in
from 1998 in which early POCD was seen in 26% of patients accordance with our findings (Table 4). Postoperative pain
1 week postoperatively.23 The ISPOCD study included levels do not only affect opioid administration, but also
numerous patients undergoing hip and knee replacement, have an impact on rehabilitation and sleep.29,30 Sleep, pain,
and at 1 week, POCD was found in 57 of the 303 orthopedic opioids, and inflammation are part of an intricate circle of
patients tested (18.9%) and in 10.8% (31 of 287) at 3 months. interactions, where sleep disruptions may cause hyperal-
More recent studies have reported incidences of 20% to gesia which increases demand for opioids and opioids in
40% when testing at 1 week after surgery.22,24–26 Despite the themselves disrupt sleep.31,32 Several studies have illus-
differences in methods, our results are significantly lower trated a connection between sleep and cognitive abilities,
than this. Unfortunately, it is very difficult to compare these where the elderly experienced prolonged cognitive effects
findings in an optimal way, as details related to the periop- due to sleep deprivation.33,34 Sleep architecture and duration
erative care have not routinely been reported.22 As we have are negatively affected by pain, opioids, and inflammation,
previously hypothesized, we believe these factors play a all factors that play a role in the immediate recovery period.
significant role in the development of cognitive decline, and We only evaluated sleep subjectively with a question- naire
it is most unfortunate that such basic perioperative data are that may not have been the most reliable way to assess
lacking in otherwise well-conducted studies, which makes sleep architecture and quality, since there tend to be
direct comparison problematic.5,7 It seems that the fast-track discrepancies between objective and subjective sleep data.
approach had an impact on the patients’ cognition early However, obtaining objective sleep data from >200 patients
on, but is less important for late-onset POCD. Which fac- with electroencephalography over a sustained period of
tors play a role for later development of cognitive dysfunc- time is not feasible. Nevertheless, our more specific electro-
tion after surgery are unclear and are probably also harder encephalography and actigraphy studies, in smaller groups
to assess than early POCD, since several other factors may of fast-track TKA and THA patients, have shown a signifi-
influence POCD during the longer time interval. cant disturbance in sleep architecture immediately after
The average duration of surgery was about an hour, surgery,35,36 with rapid eye movement sleep being almost
with very little variation, which is probably a result of the absent on the first postoperative night but normalized
surgeons’ high level of experience and the standardization about 2 days after discharge. This may be relevant since a
of the approach. THA was performed using the posterior normal sleep pattern is important for intact cognitive abili-
approach and mainly uncemented, with incisions <15 cm. ties, and even a short period of disturbed sleep pattern and
TKA was performed using an anterior midline approach lack of rapid eye movement sleep during the first or second
in all cases. Incision length was 10 to 15 cm, and cemented postoperative night may contribute to early postoperative
and uncemented implants were used. Duration of surgery is cognitive decline.
well below that of previously reported studies27 and reflects A limitation of our study is that the contribution of each
the fact that only consultant-level surgeons performed the element in the fast-track approach cannot be analyzed in
operations, resulting in a low level of blood loss and post- detail. However, this study is the first to comprehensively
operative complications. This, combined with the other report on such a uniform cohort of elderly patients and ren-
optimized perioperative factors (analgesic regime, intense der new knowledge on early-onset POCD after major sur-
ambulation, and short LOS) may very well have been a fac- gery in a standardized approach. The results of an enhanced
tor in the low incidence of early POCD. recovery in early cognitive dysfunction is in accordance with
Our results showed a tendency for a higher preoperative other functional improvements in the fast-track approach.37
MMSE score in the group who developed early POCD (P = The data analysis included a consideration of the practice
0.06) which is in contrast to earlier studies showing a low effect, based on data from the large community-dwelling
preoperative cognitive reserve to predispose to POCD.9,24 In age-matched control group. Optimally, the control group
line with previous studies that found increasing age to pre- needs to be matched to the patient cohort as much as pos-
dispose to cognitive changes after major surgery, our results sible, regarding age, comorbidity, cognitive reserve, etc.
also showed a tendency for increasing age to be a risk factor The fact that our control group was community-dwelling
for early POCD, while not statistically significant, the wide healthy elderly people may have affected their cognitive
95% CI does not exclude the presence of a difference between performance, and they may have performed better than
groups. This increased sensitivity to cognitive changes with our patient group. However, the aim of the cognitive test-
increasing age may have been due to a wide spectrum of ing of the controls was not to gather data on their absolute
factors. Changes in environment and disturbances in daily cognitive performance but to gather information on the
rhythm have been shown to have a greater impact on the practice effect with repeated cognitive testing. As such, we
elderly. Furthermore, the intrinsic factors of the immediate believe that the data collected from our healthy control give
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