This case-controlled interventional study involving healthy volunteers was reviewed and approved by the University of Nottingham Research Ethics Committee (reference #: N14082014 SoM GI Surgery NDDC).

We recruited healthy volunteers aged >18 years. Volunteers with pre-existing cognitive impairment (either a pre-existing diagnosis of dementia or poor performance in baseline tests), smokers, those unable to read or understand English, those with visual impairment, or those who refused to give written informed consent were excluded from our study.

After practicing each test 3 times (to allow for the learning effect of repeated tests), a baseline performance for each cognitive function task was recorded while sitting for 1-back, 2-back, and 3-back task; Stroop test; and LDT.

The volunteers were then placed in the Trendelenburg position at 17° head-down for 3 hours, moved to supine position for 1 hour, and then asked to sit up. The above tests were then repeated after 30 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours (volunteers were moved to supine position after 3 hours, so these tests were performed immediately after volunteers moved to supine position), 3.5 hours, and 4 hours (after 4 hours, the volunteers were asked to sit up in a chair, and the tests were performed immediately after they sat up; Figure 1). Between 90 minutes and 2 hours, 5 of the volunteers took a “toilet break.” The duration of toilet breaks ranged between 2.5 minutes and 4.8 minutes including walking to and from the toilet. This break was unavoidable because our volunteers were awake.

To allow for the continued learning effect that may mask the cognitive decline, a control group was recruited to provide control data for analysis. Accordingly, 5 volunteers repeated each test 4 times. Each test was analyzed individually, and the mean and SD values were calculated for a change in both accuracy and response time (RT) between the third and fourth attempt of the tests. The mean change was taken to represent the learning effect for the tests, which is known to occur when the same tasks are repeated multiple times.

Our study showed a decline in the cognitive function of participants following Trendelenburg positioning. Each volunteer’s cognitive function was assessed at various time points against his or her own baseline cognitive performance. The overall percentage of volunteers with cognitive decline increased to 40% (6/15) after 3 hours in the Trendelenburg position. After 1.5 hours, 33% (5/15) had cognitive decline, but this reduced to 27% (4/15) after 2 hours. This could be due to adaptation to being placed in the Trendelenburg position as per the Monroe-Kellie doctrine or possibly due to 5 of the 15 volunteers requiring a toilet break between 90 minutes and 2 hours into the test [17].

Once the participant sat up (after 3 hours in the Trendelenburg position and 1 hour in supine position), the initial tests revealed another slight increase in the number of participants with overall cognitive decline from 33% (5/15) to 40% (6/15). Many physiological changes initially occur in an individual when sitting from a supine position. Deegan et al recruited 19 healthy volunteers and induced transient hypotension while in both the seated and supine positions and measured mean arterial pressure and cerebral blood flow in the middle and anterior cerebral arteries along with cerebral autoregulation response. They found that autoregulatory responses were worse in the seated position in both the anterior and middle cerebral arteries, which was thought to be due to the hydrostatic gradient that occurs when in a seated position [18]. Previous studies have shown that cerebral autoregulation is dependent on vascular tone [19]. Deegan et al found that a drop in cerebral perfusion pressure leads to dilatation of the cerebral vessels, which results in reduced cerebral vascular resistance. They also looked at the theory of reduced cerebral perfusion pressure resulting from a shift in the autoregulatory curve to the right. However, the subjects included in their study did respond with an increased heart rate, suggesting a sympathetic response that should result in vasoconstriction and, therefore, an increase in cerebral vascular resistance [18]. This could explain the increase in the percentage of volunteers with cognitive decline that occurred at time point 8.

A break was taken by some volunteers between time points 3 and 4, which lasted for a maximum of 5 minutes. The volunteers then returned to the Trendelenburg position. This break could explain the reduction in the percentage of volunteers with cognitive decline at time point 4. The resulting reduction in cognitive decline that may have occurred following a short period in the upright position was comparable to the worsened cognitive decline that occurred when in the sitting position, which further supports the reduced cerebral perfusion pressure that has been shown to occur when in the seated position versus the standing position. Patients undergoing left-sided laparoscopic resections are often placed in either a modified lithotomy position (with the legs slightly flexed) or the Lloyd-Davis position. Further studies to reassess the response of a standing or head-up tilt position on recovery of cognitive function would be of clinical benefit.

There were limitations to this study, which included a bathroom break that may have affected the results achieved at time point 4. Test fatigue could also be a contributing factor, with repetitive tests being conducted in such a short time period. A repeat set of tests 24 hours after the end of the study would possibly have been beneficial for assessing the clinical impact.

A further limitation is the lack of a clear definition for POCD. ISPOCD is the largest study in this area so far, but it treats POCD as a binary definition. The clinical implications and impact on daily life of these definitions need to be further evaluated and defined along with standard tests that should be used. The high percentage of cognitive decline could be due to the sensitivity and number of the cognitive tests that were used in our study.

The results of our study indicate that Trendelenburg positioning leads to cognitive decline. A finding of potential clinical significance was that when the volunteers sat up from supine position, there was an increase in the number of volunteers with cognitive decline. This suggests that in a clinical setting, simply reducing the tilt of the table when the patient is in the modified lithotomy or Lloyd-Davis position may not be beneficial as this would most likely mimic the physiology of sitting and could further impair cognitive function due to reduced cerebral vascular resistance [18]. Further studies to assess the effect of a “break from the Trendelenburg position” while in the modified lithotomy or Lloyd-Davis position versus supine position would be clinically relevant.