Langenbecks Arch Surg (2015) 400:513–516 DOI 10.1007/s00423-015-1297-8

ORIGINAL ARTICLE

Delirium in fast-track colonic surgery Sorel Kurbegovic & Jens Andersen & Lene Krenk & Henrik Kehlet

Received: 13 November 2014 / Accepted: 3 March 2015 / Published online: 13 March 2015 # Springer-Verlag Berlin Heidelberg 2015

Abstract Background Postoperative delirium (PD) is a common but serious problem after major surgery with a multifactorial pathogenesis including age, pain, opioid use, sleep disturbances and the surgical stress response. These factors have been minimised by the Bfast-track methodology^ previously demonstrated to enhance recovery and reduce morbidity. Methods Clinical symptoms of PD were routinely collected three times daily from preoperatively until discharge in a welldefined enhanced recovery program after colonic surgery in 247 consecutive patients. Results Total median length of hospital stay was 3 days. Seven patients (2.8 %) developed clinical signs of PD most within the first 72 postoperative hours and only 1 patient with PD extending to 120 h postoperatively. Only 1 PD patient required treatment with serenase. PD patients were older (83 vs. 73 years) and had longer median stay (6 vs. 3 days). No difference in development of PD between open and laparoscopic operation could be demonstrated. Among the 7 patients with PD, 3 of these patients had later surgical complications. One patient had a subsequent strangulated small intestine, another an anastomotic leakage complicated by a bleeding gastric ulcer and death on day 12 and 1 with fever, abdominal pain and suspected but disproven anastomotic Sorel Kurbegovic and Jens Andersen contributed equally to this work. S. Kurbegovic : L. Krenk : H. Kehlet (*) Section of Surgical Pathophysiology, Rigshospitalet Copenhagen University, 4074, Blegdamsvej 9, 2100 Copenhagen, Denmark e-mail: [email protected] S. Kurbegovic : L. Krenk : H. Kehlet The Lundbeck Foundation Centre for Fast-track Hip and Knee Replacement, Copenhagen, Denmark J. Andersen Department of Surgical Gastroenterology, Hvidovre University Hospital, Copenhagen, Denmark

leakage (stay 21, 12 and 22 days, respectively). The remaining 4 PD patients stayed 4, 4, 5 and 6 days with an uncomplicated course. Conclusions These data support that an enhanced postoperative recovery program may decrease the risk and duration of PD after colonic surgery. Keywords Postoperative delirium . Colonic surgery . Fast-track surgery . Enhanced recovery program

Introduction Postoperative delirium (PD) and more subtle early and late postoperative cognitive dysfunction (POCD) are welldocumented undesirable sequelae in major surgery, especially in elderly patients [1]. Although the topic has received major attention in the last decade, a summary of previous studies on strategies for perioperative interventions to decrease delirium has largely been inconclusive [2, 3]. However, there is agreement that several non-modifiable factors may contribute to PD and POCD such as high age, limited preoperative cognitive function and chronic pain [1]. When it comes to modifiable factors, the type of anaesthesia may not be important [1–3]. Others have hypothesised that PD and POCD is a multifactorial problem influenced by acute postoperative pain, opioid use, sleep disturbances and the inflammatory responses [4], all of which are potentially modifiable and interrelated in the postoperative phase. At the same time, several efforts have been made to enhance postoperative recovery according to the Bfast-track methodology,^ which include patient information and involvement in the early recovery phase, optimised opioidsparing multimodal analgesia, optimised fluid management, early mobilisation and oral feeding all of which have been

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shown to be successful to enhance recovery and decrease postoperative morbidity across surgical procedures [5, 6]. Unfortunately, few studies have focused on the risk of PD and POCD in a fast-track surgical setting, but the first study in colorectal surgery has shown a low incidence of PD [7] and the same positive findings were found within the setting of fast-track hip and knee arthroplasty [8, 9]. The aim of the present retrospective analysis of prospectively collected data from a well-established fast-track colorectal unit [10] was therefore to assess the incidence and severity of PD in a large consecutive cohort in fast-track colonic surgery.

Patients and methods Patients Elderly patients (range 60–94 years) undergoing elective colonic surgery at Copenhagen University Hvidovre Hospital from January 7, 2010 to December 27, 2012 were extracted from a prospective database. A total number of 259 consecutive patients was registered but 12 cases were excluded due to incorrect social security number (n=8) or inadequate record (n=4), leaving a total of 247 patients eligible for analysis. The fast-track methodology Perioperative management followed the principles of fasttrack colonic surgery described in detail before [10, 11]. In summary, the program included detailed preoperative patient information about the care principles, no bowel preparation except for a 240-ml natriumducosate enema (klyx®; Ferring, Copenhagen, Denmark) in the evening and morning before surgery. The patients were operated during combined general anaesthesia (no premedication, remifentanil 1 μg/kg/h, propofol 3 mg/kg/h, cisatracium 0.15 mg/kg, ondansetron 4 mg and i.v. ketorolac 30 mg) and thoracic epidural analgesia (bupivacaine 0.25 % 4 ml/h and morphine 0.2 mg/h), using transverse or curved incisions or a laparoscopic approach. A nasogastric tube was removed at the end of operation, drains were not used routinely and urinary bladder and epidural catheters were removed 24 and 48 h postoperatively, respectively. Oral analgesia consisted of paracetamol 1 g/6-hourly and ibuprofen 600 mg/8-hourly and only opioids on request. Free solid food intake was initiated from the day of surgery, and mobilisation initiated on the day of surgery following a welldefined nursing care program [10]. Fluid management secured no fluid overload and discharge was planned on the third postoperative day (72 h postoperatively) [11]. Discharge criteria were normalisation of gastrointestinal function with normal fluid and food intake, sufficient pain relief on oral

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analgesics and patient acceptance. All patients were seen in the outpatient clinics 30 days postoperatively. Mental function was assessed by the nurses based upon the confusion assessment method (CAM) [12] with an algorithm including four features: (1) acute onset and fluctuating course, (2) inattention, (3) disorganized thinking and (4) altered level of consciousness. The diagnosis of PD requires the presence of features 1 and 2 and either 3 or 4. The nursing staff routinely evaluated the patients three times daily (each nursing shift) starting on the day before surgery (baseline) up to the fourth postoperative day (POD 4) or discharge day using a standardised care plan including cognitive evaluation. To ensure consistency and accuracy and to eliminate bias among nursing staff, these have been instructed to note and specify any onset compared to baseline. All patient records were screened for patients meeting the CAM criteria for PD. Data processing was done by IBM® SPSS® statistic 22 and presented as absolute or relative numbers and with median or mean values where appropriate. Continuous data were compared with Mann-Whitney test and Fisher’s test when comparing PD and type of surgery. P < 0.05 was considered significant.

Results Seven patients (2.8 %) of the 247 patients fulfilled the CAM criterions [12] for PD. Five patients fulfilled features 1, 2 and 3. Two patients fulfilled features 1, 2, 3 and 4. Patient demographics in patients with or without postoperative PD are shown in Table 1. Median (range) postoperative LOS in the total group was 3 (2–45) days. The PD patients were older and with a longer postoperative stay but otherwise did not differ Table 1

Patient characteristics. Values are median (range) [mean] Overall (n=247)

Age Gender Male Female LOS (days) Surgical procedure Right hemicolectomy Sigmoid resection Hartmann reversal Left hemicolectomy Surgical technique Laparoscopic Open surgery

+ Delirium ÷ Delirium P value (n=7) (n=240)

73 (60–94) 80 (79–93) 73 (60–94) <0.001 [73.3] [83.0] [73.0] 125 122 3 (2–45) [4.8]

5 2 6 (4–22) [10.6]

120 120 3 (2–45) [4.6]

139 83 6 19

3 4 0 0

136 79 6 19

166 81

6 (3.6 %) 1 (1.2 %)

160 80

<0.001

=0.432

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from those without delirium (Table 1). In 6 of 7 patients with PD, it lasted within the first 48 postoperative hours (Fig. 1) and only 1 patient had signs of PD up to POD 4 (120 h). The duration of PD was limited to 1 day in 4 cases, 2 days in 2 cases and 4 days in 1 case. Only 1 patient received treatment for PD (one dose of serenase 4 mg). There was no difference in PD between open and laparoscopic procedures (Table 1). Among the 7 patients with PD, 1 patient had a LOS of 21 days due to reoperation for a strangulated small intestine, another stayed 12 days due to anastomotic leakage complicated by bleeding gastric ulcer and death and 1 with LOS of 22 days because of suspected but not proven anastomotic leakage. None of these conditions could be related to the previous transient PD. The remaining patients with transient PD stayed 4, 4, 5 and 6 days with an otherwise uncomplicated stay.

Discussion PD is a serious complication most often appearing in major procedures, elderly patients and unfortunately with no definitive strategies for prevention [1–3]. The reported incidence is variable often because mixture of several types of surgery, but in colonic surgery an incidence of 13 % [7] and 9 % in esophageal surgery [13] have been reported. Since the pathogenesis has been hypothesised to include pain, opioid use, sleep Fig. 1 Day of clinical signs of PD in seven of 247 patients undergoing fast-track colonic surgery. Six patients showed PD within the first 48 postoperative hours and resolution of PD occurred within 72 h postoperatively in all but one patient. Upper figure shows the number/fraction of PD patients. Lower figure shows the presence of PD in the individual patients over time

disturbances and the inflammatory response to surgery [4], studies on the effect of Bfast-track^ or Benhanced recovery^ programs are of interest, since these imply optimised multimodal non-opioid analgesia, early mobilisation and feeding and with subsequent reduction of length of stay and return to home [5, 6]. Unfortunately, only 2 procedure-specific studies are available, but both showing that an enhanced recovery program may reduce clinical delirium [7, 8]. Thus, a fasttrack program in elderly patients undergoing colonic surgery reduced length of stay from 13 to 9 days and PD from 12.9 to 3.4 % as well as a reduced IL-6 response [7]. In fast-track hip and knee replacement, there were no cases of delirium with a median LOS of 2 days in 225 patients [8] compared with a usually reported incidence of 4–10 % [4, 8]. The present study is with a more well-defined fast-track setup in colonic surgery [10, 11] and a much shorter overall LOS than reported in the Chinese fast-track colonic study [7] (mean LOS 4.8 vs. 9.0 days), but with an almost similar incidence of delirium of 2.8 vs. 3.4 %. Taken together, however, and compared with existing literature in abdominal procedures [1–3, 13], these data strongly support the benefit of a fast-track concept to reduce PD. These positive studies should lead to further detailed studies on the interaction between acute pain, opioid use, sleep disturbances and the inflammatory response in relation to a fast-track setup in a procedure-specific setting [4]. In this context, the use of a single preoperative high-dose glucocorticoid which reduces movement-induced pain, the Postoperative delirium

10.0% 9.0% 8.0% 7.0% 6.0% 5.0% 4.0% 2,0% (N=5)

3.0% 2.0% 1.0%

0,4% (N=1)

1,6% (N=4)

0,4% (N=1)

0,4% (N=1)

72-96 h (POD3)

96-120 h (POD4)

0.0% 0-24 h (POD0) 24-48 h (POD1)

48-72 h (POD2)

Pt 1 Pt 2 Pt 3 Pt 4 Pt 5 Pt 6 Pt 7 POD0

POD1

POD2

POD3

POD4

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inflammatory response and early fatigue [14, 15] and other procedures [16] may be interesting. However, recent studies in cardiac surgery did not show any improvement in postoperative cognitive function [17], which, however, may not argue against further studies, since cardiac surgery may include other specific risk factors for postoperative delirium and cognitive dysfunction [17]. In conclusion, this fast-track colonic study confirms that postoperative delirium may be reduced calling for more detailed studies on the involved pathogenic factors. Compliance with ethical standards The study did not require ethical approval according to Danish regulations, since the project was a quality assurance study on routine care. The study was approved by the Danish Data Inspection (2013-41-1676). Funding The study was sponsored by a grant from the Lundbeck Foundation [R25-A2702]. Conflicts of interest None.

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