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. 2014 Apr 18;16(9):864–869. doi: 10.1111/hpb.12266

Incidence and risk factors of delirium in patients post pancreaticoduodenectomy

Tom K Gallagher 1,✉, Sarah McErlean 1, Aimee O'Farrell 1, Emir Hoti 1, Donal Maguire 1, Oscar J Traynor 1, Kevin C Conlon 1, Justin G Geoghegan 1
PMCID: PMC4159461  PMID: 24750484

Abstract

Background

Post-operative delirium is an important and common complication of major abdominal surgery characterized by acute confusion with fluctuating consciousness. The aim of this study was to establish the incidence of post-operative delirium in patients undergoing a pancreaticoduodenectomy and to determine the risk factors for its development.

Methods

From a prospectively maintained database, a retrospective cohort analysis was performed of 50 consecutive patients who underwent a pancreaticoduodenectomy at the National Surgical Centre for Pancreatic Cancer in St. Vincent's University Hospital, Dublin and whose entire post-operative stay was in this institution, between July 2011 and December 2012. Two independent medical practitioners assessed all data and delirium was diagnosed according to criteria of the Diagnostic and Statistical Manual Disorder (DSM), fourth edition. Univariate and multivariate analyses were performed.

Results

Seven patients (14%) developed post-operative delirium. The median onset was on the second post-operative day. Older age was predictive of an increased risk of delirium post-operatively. Those who developed delirium had a significantly increased length of stay (LOS) as well as a significantly increased risk of developing at least a grade 3 complication (Clavien-Dindo classification).

Conclusion

This study demonstrates that post-operative delirium is associated with a more complicated recovery after a pancreaticoduodenectomy and that older age is independently predictive of its development. Focused screening may allow targeted preventative strategies to be used in the peri-operative period to reduce complications and costs associated with delirium.

Introduction

Pancreatic adenocarcinoma is arguably one of the most challenging of human malignancies. Five-year survival data from around the world remain very poor with surgery offering the only chance of a cure. Approximately 15–20% of patients present with disease amenable to surgical resection but even among this cohort, only 18–22% will be alive at 5 years.1 It is therefore incumbent upon pancreatic surgeons and oncologists alike to not only strive towards an improved survival profile but also to improve the quality of treatment and minimize the impact this treatment has on the individual's quality of life.

The procedure of a pancreaticoduodenectomy has been refined and well described over many years.2–6 The mechanisms and acceptable rates of potential complications after pancreatic surgery, including pancreatic fistula, bleeding, gastroparesis, wound and cardiorespiratory compromise have been defined throughout the literature,6,7 as they have with many other major intra-abdominal procedures.8,9 However, the recognition and study of post-operative delirium, as an independent complication, is a relatively recent development in some surgical fields including oesophageal10,11 and cardiothoracic surgery.12–14 Narrowing this down to the field of pancreaticoduodenectomy, a literature search for the terms ‘post-operative, delirium, abdominal, surgery’ revealed a total of only 36 search items in Embase, MEDLINE (Pubmed) and Cochrane library and whereas replacing the term abdominal with pancreatic reveals only two search results, both of which are related to pancreas transplantation. To our knowledge, the incidence of post-operative delirium after a pancreaticoduodenectomy has not been specifically investigated to date.

Delerium is defined as a disturbance of consciousness with reduced ability to focus, sustain, or shift attention. This change in cognition or the development of a perceptual disturbance cannot better accounted for by a pre-existing, established, or evolving dementia. The disturbance develops over a short period of time (usually hours to days) and tends to fluctuate during the course of the day. The Diagnostic and Statistical Manual Disorder (DSM) 4 definition requires that there is evidence from the history, physical examination, or laboratory findings that the disturbance is caused by a medical condition, substance intoxication, or medication side effect.15 In the case of post-operative delirium, the cause can be identified as the occurrence of the procedure itself. It is a serious and potentially harmful occurrence in the post-operative period and the aim of this study was to determine whether its onset in this particular cohort of patients is associated with a deleterious outcome.

Patients and methods

Patients

All patients undergoing a pancreaticoduodenectomy for both benign and malignant disease in the National Surgical Centre for Pancreatic Cancer in St. Vincent's University Hospital, Dublin between July 2011 and December 2012 were included in this study. In total, 107 patients were admitted and underwent a pancreaticoduodenectomy during this period. Because of unit stratification, not all post-operative care was carried out in St. Vincent's University Hospital, and so patients whose entire post-operative care, or at least the first 14 days post-operatively, was not carried out in St. Vincent's University Hospital were excluded from the study. In total, 50 patients were enrolled in the study. All patients underwent pre-operative consultant surgical and anesthetic assessment and all were presented and discussed at the units' weekly pancreatic multi-disciplinary conference. The clinical ethics review board of St. Vincent's University Hospital approved this study.

Post-operative care

In relation to analgesia, the unit protocol was for all patients to have wound catheters placed in the transverses abdominus plane for the continuous infiltration of plain levobupivicaine, and these were left in place for a minimum of 72 h. All patients additionally had pre-operative placement of an epidural catheter as well as patient-controlled analgesia.

Unless there was a requirement for an intensive care setting post-operatively, all patients were transferred to a dedicated hepato-pancreato-biliary high dependency unit for the first night and then subsequently stepped down to a dedicated surgical ward when deemed fit for transfer by both the anaesthetic and surgical services. The median length of stay (LOS) in the high dependency unit was 18 h. Once on the regular surgical ward, patients were encouraged to mobilize as tolerated and were allowed return to oral intake depending on the operating surgeons' instructions. Complications were graded according to the Clavien–Dindo classification.16

Data collection

Pre-, peri- and post-operative demographic, surgical and clinicopathological data, based on reported predictive factors for delirium, were listed by the first author and recorded by two independent medical practitioners in a retrospective manner from a prospectively maintained database. Delerium was diagnosed according to the criteria in the fourth diagnostic and statistical manual of mental disorders.15 All patients' charts were systemically reviewed by two independent reviewers for each day of the patients admission for key words that would contribute to the diagnosis of delirium whether a formal diagnosis had been made or not while the patient was an inpatient. Data were analysed from day of admission until day of discharge.

Statistical analysis

Continuous variables were analysed using the Student's t-test or Mann–Whitney U-test and categorical variables were compared using the chi-squared or Fisher's exact test. All analyses were performed using GraphPad Prism version 6.00 for Windows, GraphPad Software, La Jolla, CA, USA, http://www.graphpad.com, except for the multivariate analysis, which was performed using SPSS version 20.0 (IBM SPSS Statistics for Windows, Version 20.0; IBM Corp. Armonk, NY, USA). Statistical significance was assumed at P < 0.05. Variables that were significant on univariate analysis were entered into the multivariate analysis to estimate the delirium risk post-operatively.

Results

The 50 patients in this study comprised 31 males and 19 females, with a mean age of 62.7 years (range 41–83). There were no significant differences in the mean age between males and females. Pre- and intra-operative demographics are detailed in Table 1. Of the fifty patients, two patients (both of whom did not develop delirium) had failed epidural placement, otherwise analgesia was standardized amongst the entire cohort, as described in the Methods. A total of six patients required ICU care in the immediate post-operative period (one in the delirium group and five in the no-delirium group) but this was not statistically significant.

Table 1.

Demographics, pre-, intra- and post-operative data in patients with and without delirium

Delirium (n = 7) No delirium (n = 43) P-value
Age (y) 70.29 ± 2.95 61.47 ± 1.31 0.01
Gender (M/F) 4/3 27/16 0.77
Medical history
  Alcoholisma (number of patients) 1 7 1.00
  Chronic smoking (number of patients) 3 24 0.71
  ASA 2 vs. ASA 3 4/3 26/14 0.75
Previous psychiatric history
  Any psychiatric diagnosis (patient number) 3 9 0.33
  Previous diagnosis of depression 3 4 0.04
Pre-operative blood test
  Creatinine (μmol/l) 83.81 ± 5.35 87.86 ± 9.25 0.77
  Haemoglobin (g/dl) 12.36 ± 0.37 12.97 ± 0.28 0.46
  Albumin (g/l) 33.30 ± 1.12 34.43 ± 1.81 0.69
  Bilirubin (μmol/l) 59.86 ± 33.6 69.58 ± 21.0 0.86
  Blood loss (ml) 1128 ± 188 1475 ± 98.3 0.18
  Length of procedure (min) 365.7 ± 11.3 343.0 ± 7.30 0.23
  Admission to ICU directly post-operatively 1 5 1.00
Post-operative creatinine (day 1, μmol/l) 75.84 ± 4.24 73.00 ± 7.96 0.79
Post-operative white cell count (day 1, ×103/μl) 13.62 ± 2.94 14.23 ± 1.55 0.59
Post-operative white cell count (day 2, ×103/μl) 14.1 ± 2.02 13.87 ± 1.82 0.64
No. of Post-operative hypoxic episodesb 2 7 0.51
Lower respiratory tract infections 3 12 0.79
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a

Alcholoism was defined as consuming an estimated weekly intake of more than 21 units per week for males and more than 14 units per week for females.

b

Post-operative hypoxic episodes – defined as PaO2 < 10 kPa on arterial blood gas, the measurement of which was triggered by any oxygen saturation reading <90% and not responding to simple measures.

Four patients had a benign diagnosis pre-operatively and four of the remaining 46 (8.6%) patients were found to have benign disease on histological examination of the resected specimens (three chronic pancreatitis and one intraductal papillary mucinous neoplasm in the uncinate process). All remaining resections were for primary pancreatic adenocarcinoma.

Delirium occurred in seven patients (14%) with four occurring on the second post-operative day, 2 on the third day and 1 on the fourth post-operative day. All occurred when the patients were back on the standard surgical ward. On retrospective review of the notes, the first identification of five of these cases was by the nursing staff on night duty, by the physiotherapist in one case and by the surgical team in one case. Once recognized, all patients were managed according to recognized protocols for the management of delirium. Table 2 illustrates a summary of our integrated clinical pathway for the management of delirium in St. Vincent's University Hoptial;3 seven of the delirium patients required lorazepam (0.05 mg/kg up to 6 hourly doses) in addition to non-pharmacological management. All patients were subsequently reoriented according to nursing protocol. Three cases resolved within 72 h of onset whereas three cases took between 3 and 5 days to resolve completely. The remaining case developed severe multi-organ failure and sepsis and accounted for the single mortality in our series.

Table 2.

Integrated care pathway for patients satisfying criteria for the diagnosis of delirium

  • Identification of delirium using established diagnostic criteria (DSM 4)

  • Assessment of patient's pre-admission cognitive, functional and social status. This information may need to be clarified with the carer.

  • Identification of risk factors such as dementia, severe illness, sensory impairments, alcohol use.

  • Identification of underlying cause (commonly infection or drugs).

  • Treatment of underlying cause or removal of offending drugs.

  • Avoidance of physical restraints.

  • Avoidance of major tranquillizers, where possible, but if necessary use only one drug and in the lowest dose possible (e.g. haloperidol 0.5–3 mg orally up to QDS). Review drug treatment regularly.

  • Multi-disciplinary team involvement in treatment and discharge planning.

  • Create optimum environment for care (e.g. single room, good lighting).

  • Use reality orientation techniques and rehabilitative care models.

  • Ensure adequate discharge and follow-up to avoid unnecessary readmissions and to provide support to patient and carers.

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Univariate analyses revealed that the occurrence of post-operative delirium correlates positively with older age. No significant difference was shown in operation length, blood loss, pre-operative bilirubin, creatinine or haemoglobin levels. The incidence of post-operative hypoxia (defined as PaO2 < 10 kPa on arterial blood gas, the measurement of which was triggered by any oxygen saturation reading <90% and not responding to simple measures) was not significantly different between the groups in the first 48 h. The pre-morbid diagnosis of any psychiatric disorder for which the patient was treated at any point in the previous 5 years was not significantly different between the groups but specifically, the diagnosis and treatment of depression was.

There was one mortality in this cohort (2%), who was in the delerium group, however, the incidence of death during the post-operative period was not significantly different between patients with delirium and those without. When this case was excluded from the analysis, the LOS was significantly longer in those who developed delirium. There was also a significantly increased risk in the likelihood that patients with delirium would go on to develop a grade 3 complication or higher, P = 0.02 (Table 3). The onset of these complications was, in all cases, preceded by the onset of delirium. Complications graded 3 and above in the delirium group included death (1), pancreatic fistula (1) and intra-abdominal collections unrelated to the pancreatic anastomosis (4).

Table 3.

Post-operative outcomes, including histological outcome, length of stay and the development of a Clavien–Dindo Grade 3 complication or higher compared with a grade 1 or 2

Outcomes Delerium No delirium P-value
Risk of at least C-D Grade 3 complication 6/1 9/34 0.001
Length of Stay 31 ± 11 19 ± 2 0.072
Length of stay (mortality excluded) 35 ± 13 19 ± 2 0.02
Death 1/6 0/43 0.14
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C-D, Clavien-Dindo.

Multiple logistic regression analysis using age, previous documented diagnosis of depression, any post-operative complication above a Clavien–Dindo grade 3 and LOS as variables was performed (Table 4 ). Older age and incidence of complications of at least grade 3 and LOS were significant determinants of post-operative delirium.

Table 4.

Multivariate analysis of risk factors for post-operative delirium

Characteristic Odds ratio 95% CI P-value
Age 1.042 1.02–1.10 0.001
History of depression – – 0.082
Length of stay 1.74 1.04–2.64 0.031
Complications at least Grade 3 – – 0.048
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CI, Confidence Interval.

Discussion

The recognition and treatment of post-operative delirium is critically important, as it is associated with poorer outcomes including functional decline, longer hospitalization, institutionalization, greater costs and higher mortality.17We believe that this is the first study dedicated to the incidence and impact of delirium post pancreaticoduodenectomy.

The incidence of delirium in this study was 14%, which is not an insignificant number. As with other studies of delirium, age was found to be a significant factor. This is a particularly important point to recognize because with an aging population,18 increasing indications for a pancreaticoduodenectomy as well as an increasing willingness to undertake this surgery in the elderly population,19,20 it is possible that this may be encountered on a more frequent basis. Most studies on post-operative delirium are performed exclusively in the elderly population and indeed if one excludes the population under 65 in this study, the incidence rises to 27%. The incidence of post-operative delirium has also been previously correlated with operative stress21 and it appears that this holds true in this cohort.

It is often noted that blood loss and dehydration may potentiate and exacerbate post-operative delirium, particularly in the orthopaedic setting.22,23 This was not found to be the case in our study, however, as both intra-operative blood loss and post-operative creatinine values were not significantly different between the groups. Similarly the presence or absence of hyperbilirubinaemia and hypoalbuminaemia in the pre-operative setting was not a significant factor. There were no significant differences between the groups in the incidence of post-operative hypoxic episodes at any point in the first 48 h, or return to a higher level of nursing care, which again would intuitively seem to be a pre-disposing factor to delirium.

This study demonstrated that post-operative delirium was associated with an increased rate of post-operative surgical complications, including intra-abdominal collections and lower respiratory tract infections (LRTIs). It is noteworthy that delirium preceded the clinical onset of these complications by at least 24 h in most cases. It is possible that the use of psychoactive drugs in the management of delirium may have affected the risk of aspiration, or influenced the degree to which individuals participated in chest physiotherapy and pulmonary hygiene with a consequent increased risk of atelectasis and LRTIs. However with only three out of seven delirium patients developing a documented LRTI, this is a hypothesis that is not borne out with any significance. In their study on post-operative delirium post oesophagectomy,11 Takeuchi et al. hypothesized that the occurrence of delirium leads to an increased psycho-physiological strain resulting in an increased risk of physical complications. Although this is perhaps a slightly simplistic approach, it is not without merit to think that delays in early mobilization caused by delirium may contribute further complications.

It is also worthwhile considering the opposite – although not specifically addressed in this study, it seems intuitive that the implementation of an enhanced recovery protocol may reduce the effects, if not the incidence of post-operative delirium in this setting. Non-essential catheters such as urinary bladder catheters, nasogastric tubes, or multiple intravenous access lines should be minimized because their presence is linked to an increased risk of delirium.24 Similarly, early mobilization should be encouraged as soon as it is safe to do so. Early correction of sensory deficits, for example with eyeglasses and hearing aids, should be undertaken. This allows patients to familiarize themselves with the environment and re-orientate themselves early on. It also minimizes the occurrence of misperceptions or misinterpretation of environmental cues and stimuli. Family members and loved ones should be encouraged to visit and provide a familiar and friendly environment, as well as provide appropriate orientation and stimulation to patients, and indeed this is our units policy at all possible times.

It is of course possible that the onset of delirium is simply a harbinger for the onset of infection, and we have acknowledged that delirium preceded clinical complications by 24 h in most cases. However, that is despite no significant difference in white cell count (first 2 days) or creatinine (day 1). Therefore if that is to be the argument, then these results tell us that the onset of delirium occurs early in the post-operative course, and when it occurs, should be of course treated in its own right, but should also alert the treating physician to the possibility of an underlying problem, particularly in this complex group of post-operative patients. While clearly not being predictive for the nature of physical complications, the onset of delirium should serve as a warning to the surgical team to anticipate such problems. Therefore the early recognition of delirium is of paramount importance. In this study, it was demonstrated that increased age and the presence of a previously documented diagnosis of depression are significantly different between those who develop delirium and those who do not. Given that this is heretofore an under-reported complication, it is not unreasonable then to suggest that these patients might benefit from screening both in the pre-operative and early post-operative phases using tools such as the Mini-Mental State Examination 25 or on an even easier level with the 4AT questionnaire.26

In conclusion, the onset of delirium is a serious and common problem post pancreaticoduodenectomy and possibly heralds the onset of further complications in this already complex group.

Conflicts of interest

None declared.

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