Abstract
Objectives
The aim of this prospective study was to investigate the implementation of an enhanced recovery after surgery (ERAS) programme following pancreaticoduodenectomy (PD).
Methods
Patients undergoing PD were managed according to an ERAS protocol. Outcome measures included postoperative mortality, morbidity, hospitalization and 30-day readmission rate. Key protocol targets were: nasogastric tube (NGT) removal [postoperative day (PoD) 1]; resumption of oral fluids (PoD 1); urinary catheter removal (PoD 3); high-dependency unit (HDU) discharge (PoD 3); tolerating diet (PoD 4); drain removal (PoD 5), and hospital discharge (PoD 6).
Results
Data were collected for 50 patients (24 male; median age 67 years). Rates of mortality, morbidity and readmission were 4%, 46% and 4%, respectively. The median length of postoperative hospitalization was 10 days. The proportions of patients achieving key targets were: 78% for NGT removal; 82% for resumption of oral fluids; 48% for urinary catheter removal; 82% for HDU discharge; 86% for tolerating diet; 84% for meeting mobility targets, and 72% for drain removal. One patient was discharged by PoD 6, eight patients by PoD 7, 15 patients by PoD 8 and 26 patients (52%) by PoD 10. Discharge was delayed in 16 patients for social or transport-related reasons.
Conclusions
The ERAS protocol was implemented safely. Achieving certain targets was challenging. Non-medical causes remain a significant factor in delayed discharge following PD.
Introduction
An ‘enhanced recovery after surgery’ (ERAS) programme represents an interdisciplinary model, designed with the intention of safely hastening postoperative recovery by easing the stress response. Inevitably, postoperative complications impede recovery. However, several factors other than morbidity delay recuperation in postoperative patients, namely: pain; gut dysfunction, and immobility. Rehabilitation pathways apply evidence-based principles of care, focusing on the optimization of postoperative analgesia, early feeding, and ambulation to reduce stress and organ dysfunction.1–3 Such fast-track programmes have proven very successful following various major gastrointestinal (GI) operations, including colorectal and liver resections.4–7 These ERAS pathways can accelerate recovery, decrease morbidity and reduce hospital length of stay (LoS) without compromising patient safety, whilst utilizing health resources in an optimal way.8,9
Pancreatic cancer is the fourth leading cause of cancer death in men, the fifth in women and the second most common cause of death among all GI malignancies.10–12 Pancreaticoduodenectomy (PD) remains the mainstay of surgical treatment for periampullary malignancy and offers the only chance of longterm survival. Median survival following surgery performed with curative intent for pancreatic adenocarcinoma is reported to be 11–18 months and 5-year survival lies in the range of 10–21%.13–15 Postoperative mortality risk is typically <5% in high-volume institutions,16–24 but morbidity remains high at 30–40%.24–33
Relatively few studies have assessed the implementation of an ERAS programme following PD.19,20,34–39 Some studies have reported the feasibility and effect on reducing postoperative LoS and hospital costs.20,34,35 Other works have demonstrated low morbidity, mortality and readmission rates following the implementation of fast-track programmes.19,36 However, to date, none of this has been assessed in a UK context.
The principal aim of this pilot study was to evaluate the safety and efficacy of implementing an ERAS programme for patients undergoing PD in a high-volume UK institution.
Materials and methods
From February 2010 to July 2011, 50 consecutive patients undergoing PD were managed according to an ERAS protocol. Data were collected prospectively using a standard proforma and recorded in an electronic database. This facilitated the daily recording of parameters central to the implementation of an ERAS protocol (e.g. drain volumes, drain fluid amylase levels, commencement of oral feeding, mobilization, catheter removal).
An ERAS protocol was designed by the multidisciplinary hepatopancreatobiliary (HPB) team subsequent to a review of previously published reports in the literature and the gauging of what might be achievable in a specialist HPB unit within the UK (Table 1). Targets were established for the management of patients from the evening of the day of surgery until discharge. The initial target for discharge was postoperative day (PoD) 6 following PD. The protocol utilized defined criteria for certain elements of postoperative management, such as epidural analgesia, nasogastric tube (NGT) removal, high-dependency unit (HDU) discharge, intra-abdominal drain removal, and hospital discharge (Table 2). Epidural management is summarized in Fig. 1. The ERAS protocol also included targets for mobilization, i.v. fluid reduction and withdrawal, introduction of oral fluid/diet and urinary catheter removal.
Table 1.
Protocol for the enhanced recovery after surgery (ERAS) programme
| PoD | Targets for postoperative management |
|---|---|
| 0 | Postoperative analgesia: epidural or PCA (refer to epidural management criteria) |
| Mobilization: up to sit | |
| 1 | Postoperative analgesia: oral analgesia following NGT removal |
| NGT: removed if drainage volume <500 ml (refer to NGT removal criteria) | |
| Fluid balance: allow free clear fluids; reduce i.v. fluids to 1 l/day if oral intake is >500 ml | |
| Mobilization: up to sit for 1 h | |
| 2 | Intra-abdominal drains: cut and bag drains to improve mobility |
| Mobilization: up to sit for 2 h | |
| 3 | Postoperative analgesia: stop epidural |
| Urinary catheter: remove urinary catheter when epidural is stopped | |
| Fluid balance: stop i.v. fluids if oral intake is >1 l | |
| HDU: consider discharge to ward (refer to HDU discharge criteria) | |
| Mobilization: up to sit for 2 h and short walk around bed | |
| 4 | Nutrition: solid food intake |
| Mobilization: walking for 20 min | |
| 5 | Intra-abdominal drains: fluid amylase levels of drains sent to laboratory; remove drain if amylase is <300 U/l and drain output is <100 ml (refer to drain removal criteria) |
| 6 | Hospital discharge: consider discharge if hospital discharge criteria are met |
PoD, postoperative day; PCA, patient-controlled analgesia; NGT, nasogastric tube; HDU, high-dependency unit.
Table 2.
Outline of postoperative management targets in the protocol for the enhanced recovery after surgery (ERAS) programme
| Criteria | |
|---|---|
| Epidural management | Refer to Figure 1 |
| NGT removal | • If 24-h postoperative NGT drainage is <500 ml, NGT can be safely removed and clear oral fluids initiated |
| • EXCLUSION If significant preoperative gastric outlet obstruction was present, seek consultant surgeon opinion prior to removal of NGT | |
| • If persistent vomiting is present thereafter, consider replacement of NGT | |
| DGE = NGT remains in place for >3 days or has been reinserted for persistent vomiting after PoD 3 or inability to tolerate a solid diet by PoD 7 | |
| HDU discharge | Respiratory |
| • Requiring <40% oxygen | |
| • Respiratory rate <20 and >10 breaths/min | |
| • SpO2 >95% (may be lower in patients with COPD) | |
| • Good cough reflex and cooperation with physiotherapy | |
| Cardiovascular | |
| • Not requiring ECG or CVP measurement (although CVP line may be in place) | |
| • Not requiring an arterial line, inotropes or bolus administration of fluid | |
| • Able to mobilize out of bed without need for inotropes | |
| Renal | |
| • Stable renal function, passing ≥25 ml/h urine | |
| • Urea and creatinine not increasing (confirmed on morning of transfer) | |
| Neurological | |
| • Patient alert and obeying commands | |
| Analgesia | |
| • Pain is well controlled on current method of analgesia | |
| Blood tests | |
| • Stable or improving (confirmed on morning of transfer) | |
| General | |
| • Able to mobilize out of bed | |
| Intra-abdominal drain removal | • Monitor daily drain output volumes |
| • PoD 2: drains cut and bagged to facilitate mobilization | |
| • PoD 5: assessment of drain volume nature and amylase content | |
| Drains removed if: | |
| 1 Drain volume is <100 ml | |
| 2 Fluid is clear in colour | |
| 3 Amylase is <300 IU/l | |
| NB If drain removal criteria are not met, further drain management will be at the discretion of the consultant | |
| Hospital discharge | Patients must achieve all of the following: |
| • Adequate pain control on oral analgesia | |
| • Ability to eat and drink with no requirement for i.v. fluids in previous 24 h | |
| • Independent mobility (can mobilize independently to toilet) | |
| • Ability to perform activities of daily living (washing, dressing) without help from nursing staff | |
| • Return of blood tests to normal range | |
| • Willingness to go home | |
NGT, nasogastric tube; HDU, high-dependency unit; DGE, delayed gastric emptying; PoD, postoperative day; SpO2, saturation of peripheral oxygen; COPD chronic obstructive pulmonary disease; ECG, electrocardiogram; CVP, central venous pressure.
Figure 1.
Epidural management. PCA, patient-controlled analgesia; INR, international normalized ratio; PoD, postoperative day
Patients received effective analgesia from the day of surgery in the form of epidural or patient-controlled analgesia (PCA). They followed a programme of daily mobilization, which began with getting up to sit on the evening of the day of surgery and progressed to walking for 20 min on PoD 4. The NGT was removed on PoD 1 if the drainage volume was <500 ml. Clear fluids were allowed from PoD 1 and solid food was allowed from PoD 4. Intravenous fluids were reduced to 1 l per day if oral intake was >500 ml and stopped if oral intake was >1 l. Intra-abdominal drains were ‘cut and bagged’ on PoD 2 to improve mobility. The target was to discharge patients from the HDU by PoD 3. On PoD 5, samples of drain fluid were sent to the laboratory for analysis of amylase levels. Drains were removed if the amylase level was <300 U/l and drain output was <100 ml. The aim was to discharge patients from hospital on PoD 6.
Postoperatively, patients were provided with thromboprophylaxis in the form of subcutaneous heparin (5000 U, twice daily) or subcutaneous low-molecular-weight heparin (dalteparin sodium, 2500 U, once daily, or enoxaparin sodium, 2000 U, once daily). A subcutaneous somatostatin analogue (octreotide, 100–200 mg, three times daily) was prescribed at the discretion of the responsible surgeon. All patients were prescribed an anti-emetic and acid suppression was provided in the form of either i.v. H2-receptor antagonist (ranitidine, 50 mg, three times daily) or an oral proton-pump inhibitor (lansoprazole, 30 mg, once daily).
Measures of outcome
Data were collected on: demographics; preoperative bilirubin level; indication for PD; pathology of resected specimen; type of procedure; duration of surgery; operative blood loss; all peri- and postoperative complications; readmission (within 30 days of discharge); mortality (in hospital/within 30 days of surgery); postoperative hospital LoS before being deemed medically fit for discharge (Table 2), and LoS before actual discharge.
Major surgical complications were defined as:
pancreatic fistula (PF): a drain output of any measurable volume of fluid on or after PoD 3 with an amylase content greater than three times the serum amylase level [according to the International Study Group on Pancreatic Fistula (ISGPF)];40
intra-abdominal abscess: a collection of fluid >5 cm in diameter on computed tomography or ultrasound (ISGPF definition),40
intra-abdominal haemorrhage defined according to the guidelines established by the International Study Group of Pancreatic Surgery (ISGPS).41
Minor surgical complications were defined as:
delayed gastric emptying (DGE) as indicated by an NGT that remained in situ or was re-inserted after PoD 3 (ISGPS definition).42
Results
Demographics
Fifty patients were eligible for this study and underwent PD following the introduction of an ERAS protocol. Demographic and operative data are illustrated in Table 3.
Table 3.
Patient demographics and operative details
| Categorical variable | ERAS patients, n= 50 |
|---|---|
| Age, years, median (IQR) | 67 (55–73) |
| Gender, male, n (%) | 24 (48%) |
| Indication for PD, n (%)a | |
| Head of pancreas carcinoma | 26 (52%) |
| Ampullary carcinoma | 16 (32%) |
| Distal CBD carcinoma | 3 (6%) |
| Endocrine neoplasm | 1 (2%) |
| Chronic pancreatitis | 0 |
| Other | 4 (8%) |
| Procedure, n (%) | |
| Classical PD | 42 (84%) |
| Pylorus-preserving PD | 6 (12%) |
| PD with SMV or portal vein resection | 2 (4%) |
| Duration of surgery, min, median (IQR)a | 360 (310–420) |
| Estimated theatre blood loss, ml, median (IQR)a | 1000 (604–1275) |
Data available for 48 patients.
ERAS, enhanced recovery after surgery; IQR, interquartile range; PD, pancreaticoduodenectomy; CBD, common bile duct; SMV, superior mesenteric vein.
Implementation of the ERAS protocol
Forty-three patients (86%) were commenced on epidural analgesia. In seven patients the epidural placement was unsuccessful or functioned poorly, and PCA was utilized instead (Table 4). The epidural was discontinued by PoD 3 in 42 patients; although in one patient with a prolonged prothrombin time, the epidural catheter remained in situ until PoD 4. In one patient, the epidural was not stopped until PoD 6 for reasons of opioid tolerance. Only 23 of 48 transurethral urinary catheters were removed by PoD 3. The median duration of urinary catheterization was 4 days [interquartile range (IQR): 3–5 days] and two patients were given longterm catheters.
Table 4.
Implementation of enhanced recovery after surgery (ERAS) programme protocol: key targets
| ERAS postoperative targets | Proportion of patients achieving key protocol targets |
|---|---|
| NGT removal on PoD 1 | 39 of 50 (78%) |
| Resumption of oral fluids PoD 1 | 41 of 50 (82%) |
| Tolerating solid diet PoD 4 | 43 of 50 (86%) |
| i.v. fluid support stopped PoD 4 | 25 of 50 (50%) |
| i.v. fluid support stopped PoD 5 | 36 of 50 (72%) |
| Epidural analgesia PoD 0 | 43 of 50 (86%) |
| Epidural analgesia stopped PoD 3 | 42 of 43 |
| Urinary catheter removal PoD 3 | 23 of 48a |
| Daily mobilization programme PoD 0 | 18 of 50 (36%) |
| Daily mobilization programme PoD 1 | 42 of 50 (84%) |
| Drain removal once criteria met | 36 of 50 (72%) |
| HDU discharge PoD 3 | 41 of 50 (82%) |
| Discharge from hospital PoD 6 | 1 of 50 (2%) |
| Discharge from hospital PoD 7 | 8 of 50 (16%) |
| Discharge from hospital PoD 8 | 15 of 50 (30%) |
| Discharge from hospital PoD 9 | 18 of 50 (36%) |
| Discharge from hospital PoD 10 | 26 of 50 (52%) |
Two patients had longterm urinary catheters.
NGT, nasogastric tube; PoD, postoperative day; HDU, high-dependency unit.
The NGT was removed on PoD 1 in 39 patients (78%) and in all patients by PoD 3. Patients in whom the NGT was not removed on PoD 1 had either failed to meet NGT removal criteria or were submitted to re-laparotomy. The NGT was re-inserted in seven patients (14%) because of persistent nausea and vomiting. Oral intake of clear fluids resumed by PoD 1 in 41 patients (82%) and oral solid diet was tolerated by PoD 4 in 43 patients (86%). First flatus and stool were passed at a median of PoD 4 (IQR: 3–5 days) and PoD 6 (IQR: 4–7 days), respectively. In 25 patients (50%), i.v. fluid support was discontinued by PoD 4, but this rose to 36 patients (72%) by PoD 5. Drain amylase was measured on PoD 5 in 45 patients (90%), on PoD 4 in three patients (6%) and on PoD 2 in one patient (2%). In one patient, no sample was sent. Drain removal was delayed in 14 patients (28%). Delays were most often caused by delays in obtaining fluid amylase results from the laboratory; this was especially true if PoD 5 fell at the weekend as the laboratory did not run the test during this time. Other reasons included a change in the consistency of drain fluid and clinical factors.
Only 18 patients (36%) achieved the target of mobilization on PoD 0, although 42 patients (84%) did so on PoD 1. Poor compliance reflected the fact that patients were clinically unfit (e.g. hypotensive), sedated or in pain. Forty-one patients (82%) were discharged from the HDU by PoD 3.
Postoperative outcomes
The overall in-hospital mortality rate was 4% (two patients), the morbidity rate was 46% (23 patients) and the readmission rate was 4% (Table 5).
Table 5.
Postoperative course in the enhanced recovery after surgery (ERAS) programme
| ERAS patients, n= 50 | |
|---|---|
| Postoperative LoS, days, median (IQR) | |
| All patients | 10 (8–17) |
| Patients without complications | 9 (8–10) |
| Postoperative morbidity, n (%) | 23 (46%) |
| Postoperative pancreatic fistula, n (%) | 6 (12%) |
| Delayed gastric emptying, n (%) | 7 (14%) |
| Intra-abdominal collection, n (%) | 5 (10%) |
| Intra-abdominal haemorrhage, n (%) | 4 (8%) |
| Re-laparotomy, n (%) | 5 (10%) |
| Readmission, n (%) | 2 (4%) |
| Postoperative mortality, n (%) | 2 (4%) |
LoS, length of stay; IQR, interquartile range.
The first death occurred in a 68-year-old woman who had presented with jaundice and had undergone an extended PD to include a pancreatic cyst without prior biliary decompression. She developed an anastomotic leak and sepsis 8 days postoperatively and underwent re-laparotomy. Subsequently, she developed a colocutaneous fistula and progressive organ failure and died 121 days post-PD. The second patient was a 53-year-old man who made an excellent initial recovery and was discharged on PoD 7. He was readmitted on PoD 15 with an intra-abdominal haemorrhage and underwent re-laparotomy. He suffered a fatal cardiac arrest postoperatively. Three other patients underwent re-laparotomy; in all patients the indication for re-laparotomy was severe, late (>24 h), intra-abdominal haemorrhage. Postoperative PF (POPF) occurred in six patients: one suffered Grade A POPF; four patients had Grade B POPF, and one patient had Grade C POPF. Delayed gastric emptying was the most common complication, occurring in seven patients (14%).
The median LoS for all ERAS patients was 10 days (IQR: 8–17 days). In patients without complications, the median LoS was 9 days (IQR: 8–10 days).
Hospital discharge was delayed for social or transport-related reasons in 16 patients (32%) who were considered medically fit for discharge. Discharge was delayed by 1–4 days in 14 of these patients and by ≥10 days in two patients.
Discussion
Initial results from this pilot study show the feasibility and safety of implementing an ERAS programme following PD. Mortality, morbidity and readmission rates were low. A median LoS of 10 days was in keeping with LoS data reported in other PD fast-track studies.19,36 Most of the targets were met by the majority of patients: the NGT was successfully removed on PoD 1; oral fluids and solid food were tolerated by PoD 1 and PoD 4, respectively; epidural analgesia was initiated on PoD 0 and withdrawn on PoD 3; abdominal drains were removed once criteria were met, and patients were discharged from the HDU by PoD 3. However, achieving compliance on several other targets was more challenging.
Urinary catheter removal by PoD 3 was problematic as some patients required ongoing monitoring of urine output, which was easier to assess with the catheter in situ. Although this may simplify the task for busy ward nurses, prolonged catheterization increases the risk for infection and decreases patient mobility.
Similarly, i.v. fluid support could not be discontinued by PoD 4 in a number of patients in whom oral fluid intake was insufficient. Patients may require more encouragement to take fluids orally.
Another challenge concerned the removal of intra-abdominal drains. Although for the most part drain samples were sent for fluid amylase analysis on PoD 5, it commonly took at least 1 day more for the results to become available. If PoD 5 fell at the weekend, the ensuing delays resulted in postponed drain removal. A randomized controlled trial found significantly decreased rates of PF, abdominal and pulmonary complications with early drain removal (PoD 3) compared with late drain removal (PoD 5 and later) in patients at low risk for PF (amylase values of <5000 U/l on PoD 3).43 There is still debate on whether or not drains should be routinely placed following PD and their use is based on low-level evidence.44 A revised ERAS protocol should perhaps include earlier analysis of drain fluid amylase with the target of achieving earlier drain removal.
The protocol was also limited by insufficient patient compliance with the mobilization programme. With hindsight, it is conceivable that setting a target of ‘getting the patient up to sit’ on PoD 0 was slightly idealistic because many patients were sedated postoperatively or were clinically unfit or in pain. By PoD 1, compliance had improved considerably; however, further problems arose at PoD 4, when patients were required to ‘walk for 20 min’ in order to achieve the mobilization target. Able-bodied, de-catheterized patients were able to achieve this, but several patients required intense nursing or physiotherapist input to achieve this goal and staffing and time constraints can prevent this from occurring.
Other minor issues pertaining to the clinical communication of daily targets were noted. On at least one occasion, a patient who might have tolerated solid diet by PoD 4 was refused diet because he or she was documented as being restricted to free oral fluids only.
Following this study, an aspect of the protocol that may require revision concerns the use of postoperative NGTs. Although this has not been explored exclusively in pancreatic surgery, evidence suggests that the routine use of NGTs following elective laparotomy is not warranted.45,46
A further component of this ERAS protocol was that solid food was withheld until PoD 4. There is a lack of evidence to support this and early diet has been shown to be safe following major upper GI and HPB surgery, including PD.47 A revised ERAS protocol may forgo the imposition of formal restrictions on postoperative diet in an attempt to improve upper GI function.
A study comparing epidural with i.v. analgesia post-PD suggested that thoracic analgesia is associated with a higher rate of complications as a result of haemodynamic instability.48 It is possible that haemodynamic instability may have compromised mobility and urinary catheter removal in this study through issues of hypotension and fluid management. However, there is abundant evidence to support epidural analgesia as a very effective form of analgesia following major abdominal surgery.49–53
Personal preoperative counselling targeting patient expectations is key to enhanced recovery: it helps to alleviate fear and anxiety, and explains the importance of achieving daily targets.54–56 Although the protocol was implemented in a ward familiar with ERAS programmes for liver resection patients, ERAS for patients following PD was a new phenomenon. Patients were counselled preoperatively with regard to postoperative recovery, but this could be enhanced further with additional personal counselling and the provision of specialist nurse support.
In retrospect, the target of discharge from hospital on PoD 6 was ambitious. The earliest median discharge reported in the literature was 7 days in a US study, but this has only been reported once.18 The majority of patients (52%) in this study were discharged by PoD 10, although, interestingly, nearly one third of patients were subject to delayed discharge for social or transport-related reasons. Previous studies have reported that postoperative LoS is reduced in patients on ERAS programmes compared with historical controls.20,34,35 The median LoS following the introduction of ERAS in this series is notably shorter than the 13 days reported in a historical series of 449 patients in this institution (R.W. Parks, University of Edinburgh, unpublished results). A postoperative stay of 10 days is also shorter than those reported in most published studies.34,35 In a future ERAS protocol, a target of hospital discharge on PoD 9 may be a more realistic goal in a UK health care setting as this was the median LoS for patients without complications in this study.
The reductions in LoS seen in ERAS studies for PD do not compare with the impressive reductions reported in ERAS studies for colorectal or liver resections. It could be argued that this reflects the high rate of morbidity following PD (30–40%) relative to the acknowledged lower rate of complications following colorectal and standard liver resections. A lower morbidity rate means that recovery in the majority of patients will be influenced only by gut function, pain and mobility (other than social or transport-related issues). However, in PD a smaller proportion of patients fall into this category and even they face more troublesome gut motility problems. Therefore, there is less scope to improve recovery by enhancing gut function, reducing pain and improving mobility because the high morbidity rate will overshadow any gain in functional capacity.
The postoperative morbidity rate in this series is in keeping with the results of the majority of studies.20,35–37 Without a control group, the current study cannot demonstrate a significant reduction in morbidity. One study reported a reduced rate of DGE in fast-track patients.34
In conclusion, initial results from this study show the feasibility and safety of implementing an ERAS programme following PD. Most targets were met, although some proved more challenging, particularly those relating to early mobilization and the removal of urinary catheters and abdominal drains. There were several reasons for this, including: staffing levels and time constraints; the need to monitor urine output in a proportion of patients, and delays in obtaining drain amylase results from the laboratory. Further modification of the protocol and additional education of patients and health professionals may help to improve recovery, shorten hospital stay and enhance the return of normal function.
Acknowledgments
The authors wish to acknowledge the contributions of Y. Li, J. Loan, D. McKeown, A. Adair, S. J. Wigmore, J. J. Powell and R. Ravindran, Department of Clinical Surgery, University of Edinburgh.
Conflicts of interest
None declared.
References
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