A Low Impact Approach to Infected Pancreatic Necrosis: Review of a Case Series

Abstract

Background:

Infected pancreatic necrosis develops in approximately one third of patients with necrotizing pancreatitis and can lead to significant morbidity and mortality rates. Historically, open necrosectomy has been the mainstay of management for these patients but is in itself a morbid procedure. In recent times, minimally invasive techniques have evolved to allow a less invasive approach to these patients. Percutaneous catheter drainage of infected pancreatic necrosis is a technique that has been demonstrated to be potentially useful in the treatment of this group of patients.

Patients and Methods:

The aim of this study was to review outcomes and define the technique of percutaneous catheter drainage in patients with infected pancreatic necrosis. All patients with infected pancreatic necrosis were exclusively treated with percutaneous drainage over the study period. Acute Physiology and Chronic Health Evaluation (APACHE) II score, number and size of drains, drainage technique and drain management, hospital and intensive care unit (ICU) stay, nutritional requirements, and morbidity and mortality data were evaluated for the patient group. Computed tomography (CT) scans were used to assess the progression of the disease process and the effectiveness of the treatment.

Results:

There were nine patients with infected pancreatic necrosis in this case series between 2007 and 2012, all of whom were treated with percutaneous catheter drainage alone. The median APACHE II score in the patient group was 11, with a median stay in the ICU of 3 d and median hospital stay of 41 d. On average, nine CT scans were performed per patient during the hospital admission. A median of three drains were inserted per patient, and in the course of the study, it was evident that the larger drain size was the most effective. In eight of the nine patients in the group, complications developed that were both directly and indirectly related to the pancreatitis, but were effectively managed. There were no deaths.

Conclusion:

Percutaneous catheter drainage as a stand-alone intervention is an alternative strategy for infected pancreatic necrosis and can be used with acceptable morbidity and mortality rates in this challenging group of patients.

In patients who present with severe acute pancreatitis, necrotizing pancreatitis develops in 15%–20% of patients. Necrotizing pancreatitis is defined as development of pancreatic or peri-pancreatic necrosis. Infection develops in approximately 30% of these patients and the result is often sepsis and multiple organ failure with an associated mortality rate of 8%–39% [1 –3].

In the past, the conventional treatment approach has been laparostomy and open necrosectomy with debridement of infected necrotic tissue. This was historically performed early in the disease process, although it is now recognized that delaying open treatment by 3–4 weeks after disease onset leads to better patient outcome [4,5]. The open technique often necessitates multiple surgeries for debridement with associated risk of intra-peritoneal spread of infection, difficulty with care of laparostomy post-operatively, and the morbidity of multiple laparotomies, which may increase the risk of post-operative organ dysfunction and death [6,7].

In the past two decades, less invasive alternatives to the traditional open approach have been developed; these include image-guided percutaneous catheter drainage, minimally invasive retroperitoneal necrosectomy, video-assisted retroperitoneal debridement, and transluminal endoscopic necrosectomy [8 –10]. These innovations have shown comparable rates of both morbidity and mortality and have allowed a delay in the time to open necrosectomy in those still requiring further intervention [11,12]. The aim of this study was to analyze patient outcomes using a minimally invasive image-guided percutaneous catheter drainage method of treatment with a particular focus on technique, morbidity, length of hospital stay, and mortality rates.

Patients and Methods

Patient identification and study period

We performed a retrospective observational study at the Upper Gastrointestinal (UGI)/Hepatopancreatobiliary (HPB) Service at Wellington Regional Hospital (WRH) between 2007 and 2012. Two consultant surgeons with a particular interest in UGI/HPB diseases lead the UGI/HPB Service. All adult patients (older than 17 y) who were transferred to the UGI/HPB Service with signs of infected pancreatic necrosis (IPN) demonstrated by positive blood culture or signs of sepsis and acute pancreatic or peri-pancreatic necrosis on CT scan were included in the study. Those with pseudocysts or non-infected necrosis were excluded; there were two patients who were transferred under the service who met these latter criteria.

For each identified case of IPN, clinical records were reviewed, and Acute Physiology and Chronic Health Evaluation (APACHE) II scores calculated. Positive microbiology data were assessed, and the site and type of sample and organism isolate recorded. Data were gathered from the clinical records, and because the percutaneous drainage (PD) method of intervention was used in this study, information was collected on the number of drains inserted and the size of these drains. Data were also gathered on complications of pancreatitis and their management and on the length of each patient's hospital stay. A review of each patient's nutritional status and enteral nutrition (EN) and total parenteral nutrition (TPN) received during treatment was also performed.

Computed tomography (CT)

CT scan was performed at the discretion of the consultants managing the patient's care based on their clinical condition. CT scans were assessed by consultant radiologists within WRH and reported at the time of the scan. Following data collection, the CT scans were reassessed by a consultant radiologist, with a special interest in abdominal radiology.

Treatment

Patients included in the study were treated using a combination of PD under image guidance, antibiotics, and nutrition support. This treatment is not currently defined by protocol and was evolving; it was conducted at the discretion of the treating surgeon and interventional radiologist.

Those patients who presented to WRH initially were treated as per emergency department (ED) protocol on arrival. When pancreatitis was suspected, patients were referred to the general surgical service for further investigation and diagnosis. Once a diagnosis of pancreatitis was confirmed, patients received fluid resuscitation, and further laboratory tests were performed to allow calculation of the APACHE II score to assess disease severity. Admission to the ICU for treatment was based on this score and clinical picture. Initial conservative treatment was initiated on the basis of clinical progression. If the patient's clinical status deteriorated and a diagnosis of IPN was established, the patient was transferred to the UGI/HPB Service.

Optimizing nutrition is an important consideration in the management of pancreatitis. Because modern treatment principles aim to maintain gut function [13], nutrition support was provided with escalation in a stepwise manner. A dietitian reviewed all the patients on day 1 of admission to the UGI/HPB Service, with further regular assessments. Oral intake progressed as tolerated. Because of the disease process, however, all patients went through periods of having very poor oral tolerance and required nutrition support by artificial modalities.

To supplement oral intake, each patient first received nasogastric feeding, and if unsuccessful, progressed to nasojejunal feeding, with the tube placed under fluoroscopic guidance or via endoscopically sited percutaneous gastrostomy with jejunal extension, or TPN. The TPN was used only if all other modalities were ineffective.

A percutaneous catheter was placed into the necrotic area of the pancreas, under image guidance, and drainage and irrigation were performed. The patient was assessed regularly for signs of clinical sepsis as a gauge of improvement. If a patient status was found to be deteriorating, a repeated CT scan was performed to check for progression of the necrotic area. On the basis of the scan report and the clinical condition, a decision was made by the treating surgeon on whether to escalate the drain size or to insert further drains into areas that were being ineffectively drained. With the course of time, as more experience was gained, larger drains were placed at the outset of the drainage procedure. The drains were left in situ as non-infected collections continued to drain; this avoided the re-formation of collections, which could become re-infected.

The patient and family members were trained in drain care, including monitoring output, and the patient was discharged home and treated as an outpatient. Patients were followed in an outpatient clinic within 6 weeks with a repeated CT scan to assess progression of the necrotic area. On occasion, the patient needed re-admission for further drain modification or failure to thrive. Drains were removed at the discretion of the consultant after reviewing the results of the CT scan and drain output. This tactic evolved during its use at WRH to enable improvement and modification of technique.

Antibiotic therapy was initiated in all patients included in this study; only one of these patients did not return a positive blood, drain fluid, or drain aspirate culture during admission. Initially, antibiotic agents used were cefuroxime and metronidazole, then escalating to more aggressive agents depending on the culture sensitivity and the specialist's microbiologic recommendation.

Results

During the study period, 11 cases of complicated pancreatitis were identified. Of these, 9 patients were retrospectively identified as meeting the criteria for IPN and included in this study. The study group represented a wide range of ages.

Many of the patients had underlying medical co-morbidities. Interestingly, the most notable similarity between each of the patients was an elevated body mass index (BMI), although this was not calculated for all patients.

The most common cause of pancreatitis in patients included in the study was gallstones, which were present in five of the nine patients. Alcohol was believed to be causative in two cases; however, one of these patients also had proved gallstones, and it is unclear as to which etiology led to the episode of pancreatitis. The cause of pancreatitis was idiopathic in two patients. One patient was found to have elevated triglyceride levels.

After initially being nil by mouth (NBM), all patients in the group began oral intake as tolerated. All patients were allowed oral intake as tolerated and managed oral fluids at least. Because of poor tolerance of oral intake, however, seven patients received supportive EN and five patients required TPN. Five of the patients received both EN and TPN (Table 2). Progression from EN to TPN was because of impaired gut motility, inability to tolerate the feeding, and poor feeding absorption.

Table 2.

Course of Treatment and Outcomes for Patients

APACHE II	0– 16 (11)^*
Length of admission (d)	7–117 (41)^*
No. of patients admitted to ICU	6
Length of ICU stay (d)	0– 53 (3)^*
Number of CT scans	3– 14 (9)^*
Number of drain insertions	1– 6 (3)^*
Length of time drain in situ (mo)	3– 17 (7)^*
Enteral nutrition	7
Total parenteral nutrition	5

Median.

APACHE = Acute Physiology and Chronic Health Evaluation; CT = computed tomography; ICU = intensive care unit.

Patients included in the study had APACHE II scores between 0 and 16 with a median of 11, which corresponds to a mortality rate of 15%. Patients with two of the three highest APACHE II scores, 16 and 12, had the longest stays in the intensive care unit (ICU)— 35 and 53 d, respectively. The patient with the second highest score of 14 was in ICU for only 3 d, however.

During the course of their treatment, including re-admissions, each patient had at least three CT scans with one patient requiring 14 CT scans. On average, nine CT scans were performed per patient.

Of the nine patients included in the study, all had PD of their infected pancreatic collections using radiologic guidance. Each patient had between one and six separate drain insertions during treatment; the median number of drain insertions in the group was three. The drains inserted during the first procedure ranged from 8F to 12F, with only one patient having a 24F drain inserted initially. The patient with the 24F drain from the outset required only one drain insertion to be performed.

Of the other eight patients, only one patient's disease was able to be managed with a 14F drain. Seven of the patients had a gradual increase in drain sizes to 24F or double lumen 16F. Often each patient had more than one drain, and if the drainage from the larger drain was ineffective, irrigation was commenced via the smaller drain to facilitate flow. In all patients, the drains remained in situ for between 3 and 17 mo, with a mean period of 7 mo. The data set for length of time that drains were in situ is not complete, because one patient in the group self-discharged and did not attend follow-up clinics. All other patients were able to be discharged to home with drains in situ and attend clinics for follow-up.

Table 1.

Patient Demographics and Etiology of Pancreatitis

Age	23–70 (48)^*
Gender
M	6
F	3
Background
HTN	3
Hyperlipidemia	2
IHD	1
CVA	1
DM I/II	3
Previous surgery	1
Other	8
BMI	28–37 (33)^*
Cause
Alcohol	2
Gallstones	5
Triglycerides	1
Idiopathic	2

Median.

BMI = body mass index; CVA = cardiovascular accident; DM = diabetes mellitus; HTN = hypertension; IHD = ischemic heart disease.

The length of stay during admission with IPN varied greatly, ranging 7–117 d; the median length of first admission was 41 d. During this time, six of the nine patients spent time in the ICU. The length of stay in the ICU ranged 0–53 d among all the patients included, with a median stay of 3 d in the ICU. Four patients spent 10 or more days in the ICU because of severe abdominal complications related to pancreatitis; three of these patients with the longest ICU stay underwent laparostomy or laparotomy for complications of severe acute pancreatitis such as abdominal compartment syndrome and ischemic colon.

These more traditional open approach operations were performed before transfer of each patient's care to the UGI/HPB Service and before percutaneous drain placement. Further laparotomies for re-exploration and washouts were performed as needed. None of these patients underwent open necrosectomy at any stage after PD.

Every patient had a minimum of one blood sample withdrawn for bacterial culture during his or her stay (Table 3). Of these, 63% were positive for systemic sepsis. Fluid aspirated during drain insertion and samples withdrawn subsequently from in situ drain output were sent for culture and had positive results in 75% of the cases. Only one patient within the study group did not have any positive culture results. The most common organisms grown were Enterococcus species, gram negative coliform species, and gram positive Staphylococcus.

Table 3.

Culture Results from Blood and Drain Fluid

Positive cultures
Blood	6
Drain	8
None	1

The majority of patients in the group (eight of nine) had acute complications during the episode of pancreatitis. Pancreatic fistulas developed in four patients, but all were self-limiting. Leakage around the drain site developed in two patients; the leakage was managed with local measures. Organ failure necessitating supportive care in the ICU developed in three patients. Three of these patients had acute renal failure; one patient needed dialysis and the others had fluid therapy. Acute respiratory distress syndrome developed in two patients; one patient needed a period of ventilation, and the other received continuous positive airway pressure.

In eight of nine patients, complications developed that were not directly related to the pancreatitic process but rather related to the complexity of the illness and the patients' long stay in hospital and other underlying co-morbidities. These are listed in Table 4.

Table 4.

Complications

Deep vein thrombosis	Pleural effusion
Skin graft for laparostomy wound	Ascites
Pulmonary edema	Anemia
Atrial fibrillation	Portal vein thrombosis

Medium-term complications were also encountered, with pancreatic insufficiency necessitating pancreatic enzyme replacement developing in seven patients and five patients needing insulin therapy for diabetes mellitus. The total complication rate excluding enzyme replacement was 89%.

There was no deaths in this cohort group. After complete recovery from pancreatitis and discharge from care, two patients died from unrelated causes—one of an unknown cause after discharge, and one secondary to hepatobiliary carcinoma.

Discussion

Historically, open necrosectomy has been considered the gold standard for IPN. The rationale for this dogma was multifactorial and included adherence to basic surgical principles of debridement of infection, inefficacy of antibiotic penetration, and need for early intervention [14]. Many studies have shown that the morbidity associated with surgical necrosectomy is high, with a mortality rate ranging 20%–45% [11,15,16]. Because of the advancement in imaging techniques and the advent of minimally invasive procedures with their attendant low morbidity and mortality rate, however, a low impact approach to IPN has been realized. Recently, many studies have demonstrated these minimalistic techniques to be associated with mortality rates ranging 0%–15% [8,10,17].

Among the nine patients we assessed in this study, as expected, we found a large variability in demographics and background. There was a wide variety of age groups and medical and social backgrounds among the patients. Interestingly, the most notable and common characteristic among the patients was an elevated BMI, which likely reflects the increasing incidence of this condition in Western society. The most common cause for pancreatitis in this selected group was found to be gallstones (56%) [18], followed by alcohol (22%). Each patient was thoroughly investigated to rule out other additional causes of pancreatitis. The identified causes, such as gallstones, alcohol, and elevated triglycerides were managed accordingly.

Elective cholecystectomies were performed for patients with gallstones after complete recovery from pancreatitis. Patients with alcohol-induced IPN were referred to counseling services. Anti-hyperlipidemia medication commenced for patients with elevated triglyceride levels.

The majority of patients with IPN are in negative nitrogen balance because of protein catabolism and energy expenditure. The notion that patients need to be kept strictly NBM in acute pancreatitis is grossly outdated [19], and the current standard of practice is to optimize nutrition to enhance patient recovery and outcome. From the initial day of admission to the UGI/HPB Service, the dietetic service was consulted to aid with nutritional management, and every patient in the study group began oral intake as tolerated. If there was intolerance to oral feeding, supplementation occurred where possible with EN because evidence supports EN over TPN in reducing the acute phase reaction and decreasing protein catabolism [20].

The spectrum of cultured micro-organisms in infected pancreatic necrosis may modify outcome, but there are a paucity of data concerning their effect. A detailed knowledge on the microbial spectrum could be advantageous in directing therapy to influence the overall prognosis. The microbial spectrum cultured in our cohort group is consistent with other studies and allowed a tailored but broad-spectrum antibiosis tactic [21].

In our cohort, the APACHE II score was calculated for each patient on admission to assess the severity of the acute pancreatitis. The score ranged 0–16 (median 11), with an associated mortality rate of 4%–25%. The APACHE II score aided assessment of clinical severity on admission and potential outcome. This information allowed planning and coordination of appropriate management.

On the basis of a combination of APACHE II score and clinical condition, a decision was made regarding the intensity of management—i.e., ward versus high dependency unit (HDU) versus ICU. The median APACHE II score of 11 in this cohort of patients indicated that the majority were systemically compromised and unwell with an average mortality risk of 15% [22]. We found the APACHE II score was useful to predict the need for ICU admission and potential for extended stay. The two individuals with the longest stays in ICU had the highest APACHE II scores.

Among patients not requiring ICU admission, the APACHE II scores were the lowest. One patient with an APACHE II of 14, however, required only 3 d in the ICU. Interestingly, this patient had a large 24F drain placed at the outset of his management. It may be postulated that the magnitude of his drain and the consequent efficacy of drainage of the necrosis resulted in a far less significant systemic response and improved outcome.

The median ICU stay of 3 d and median hospital stay of 41 d in this cohort of patients is encouraging given the severity of the illness and median APACHE score of 11. It is evident that in this cohort of patients, a prolonged stay in the ICU was directly related to whether a laparotomy was performed. All the laparotomies were performed before transfer to the care of the UGI/HPB Service, secondary to complications related to IPN.

The most common complication was abdominal compartment syndrome among two of the three patients. These complications led to organ failure necessitating extended ICU management. It is unclear whether a referral to the UGI/HPB Service may have improved outcome in these patients.

A delay in time to treatment increases the risk of abdominal compromise from rupture, hemorrhage or inflammation. The old adage of wait and watch is still applicable, but the timing of intervention for IPN is still under review. Most authorities suggest a delay of at least 3 wks before any intervention, whereas other groups recommend at least 4 wks to allow for the necrosum to become liquefied and develop into a walled off necrosis [23]. With the advancements in the expertise of interventional radiology and PD evolving as first-line management, however, an early interventional (or low impact) drainage approach may be feasible as an attempt to vent and drain the infection and establish “damage control” [24].

Our management tactic mandates the presence of expertise and skill in interventional radiology and relies entirely on percutaneous CT-guided drainage of the necrotic area to extricate the infected necrotic tissue. A median of four drain insertions was performed on our nine patients. Sizes ranged 8F–24F. In the initial phase of the study, a small drain was placed during the first procedure and increased in size depending on the clinical and radiologic indication. It was believed that this escalation method was preferable to starting with a very large drain. This was advocated initially to minimize the risk associated with inserting larger drains.

The majority of patients in our cohort, however, required escalation in drain size to a larger drain to facilitate effective drainage. The smaller drains were used to irrigate fluid and facilitate fluid egress via the larger drains. Interestingly, the one patient in whom we placed a large 24F drain from the outset did not require further drain insertions. Consequently, during the period of study, as the techniques and expertise developed, larger drains were placed at the outset allowing for more effective drainage and minimizing drain insertions.

These data would indicate that larger drains are more effective in treating IPN [25] from the outset; however, in practice, technical factors can render placement of a initial large drain challenging. It is evident that better egress of necrotic material portends a more rapid improvement in clinical state, and the intention should ideally be to maximize drain size with or without irrigation. The use of PD as the sole intervention for IPN has been advocated previously but is not common practice. A recent systematic review demonstrated that up to 56% of patients with pancreatic collections (both infected and sterile) were able to be treated with PD alone [26].

This review is confounded by the heterogeneity and lack of standardization of the studies, but supports our experience in that no patient in our cohort needed surgical debridement or necrosectomy. In the Patients with Acute Necrotizing Pancreatitis trial [11], a randomized trial assessing drainage with minimally invasive debridement in a graduated approach versus open necrosectomy, a subgroup of approximately 35% of the patients was able to be treated with PD alone.

All our patients were able to be discharged to home with drains in situ once they recovered clinically. This was a major benefit to this style of management when compared with previous methods. This drainage method allows patients to rehabilitate and recover at home and return to some normalcy in life, while receiving continuing treatment. We found that patients responded well to this tactic.

There were a number of complications directly attributable to this low impact method of treatment in eight of the nine patients. This resulted in a morbidity associated with percutaneous catheter drainage of 88% in the study group. This compares reasonably with surgical management by open necrosectomy, shown by a comprehensive meta-analysis to have morbidity rates ranging 30%–90% [27], although our study numbers were small. The majority of the complications in our cohort group, however, were minor and easily managed, requiring minimal and no ICU support. The three patients who required prolonged ICU admission and who sustained severe complications with organ failure were all treated by the referring teams and had not had PD of their IPN when these life-threatening complications developed. Their major complications all occurred before PD placement.

All the patients in the study group were treated successfully for infected pancreatic necrosis, based on the criteria of absence of organ failure, normalization of blood tests, and absence of signs and symptoms of sepsis. This is consistent with what has been described in other similar studies, which reported cure rates ranging 50%–100% [8,10,17]. Importantly, the mortality rate associated with PD management was zero in our cohort group. This has been the experience of other groups using similar techniques and compares favorably with a mortality rate of 20%–40% with open necrosectomy.

Conclusion

We acknowledge that this is a small cohort group and the outcomes demonstrated by this small study in addition to others [8,10,11,17], although indicating that CT-guided PD of infected pancreatic necrosis is potentially an effective management for IPN, should be interpreted cautiously. Morbidity and mortality rates associated with PD are dramatically better than those associated with open necrosectomy. The future management of IPN is likely to be minimally invasive but multimodal in its approach, thus allowing adherence to the basic principles that dictated the necessity for pancreatic necrosectomy in the past—removal of the infected material [14].

CT-guided PD allows this to be achieved in a very efficacious manner. It has been proposed that “The trail has been blazed, traffic is increasing, but the road has yet to be paved” [25]. It is clear that PD has a role in the management of IPN, but the question of whether this technique could be used as the sole interventional modality for IPN and its utility when compared with other minimally invasive techniques can only be answered by a randomized trial. There is clearly more work to be undertaken to realize the full potential of PD in the management of IPN, and a multimodal approach encompassing all options of management is likely to optimize the management and outcome of IPN.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

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