Perioperative management - Necrosectomy and continuous closed irrigation in infected hemorrhagic-necrotizing pancreatitis

The prognosis of severe acute pancreatitis is significantly determined by the bacterial infection of pancreatic necrosis. 40-70 percent of all patients with necrotizing pancreatitis develop infected necrosis. The incidence increases with the extent of necrosis and the duration of the course.

The necrosis occurring in the initial phase of severe acute pancreatitis is primarily sterile. Bacterial superinfection occurs later in the course of the disease, usually in the second to fourth week after the onset of the disease.

If acute abdominal complications occur, immediate surgical or interventional action is required.

• Hollow organ perforation
• Hemorrhage: primarily radiological interventional
• Abdominal compartment
• Infected necrosis

Proven infected necrosis (positive FNA / air in the necrosis area) in conjunction with septic complications are generally accepted indications for surgical or interventional therapy. The mortality of patients with septic complications is 30–80%. Mortality rates of up to 100% are reported if intervention is omitted in patients with infected necrosis and organ complications.

• Persistent multi-organ dysfunction syndrome

Even in the case of sterile necrosis and organ dysfunction, surgical therapy may be indicated if there is a deterioration of the clinical situation in the sense of progressive SIRS under conservative therapy. In these patients with sterile necrosis and progressive organ complications despite maximum intensive therapy (non-responders), the indication for surgical therapy is established. It remains unclear at what point a patient is defined as a non-responder. Generally, at least 6 weeks of conservative therapy in an intensive care unit are required here.

• Fulminant acute pancreatitis -> surgery as a last resort!

Patients with fulminant acute pancreatitis represent a rare course. Here, despite intensive therapy, rapid progressive organ failure occurs within the first days of the disease. In these cases, early surgical therapy is considered a treatment option. Unfortunately, neither surgical nor conservative therapy can significantly improve the poor prognosis in this disease course.

Surgical Technique:

The goal of the surgical procedure is to clear the infection focus. The procedure should be performed later rather than sooner, preferably 3-6 weeks after the onset of symptoms! Whether minimally invasive or conventionally open depends on the extent of the necrosis.

• Open approach with necrosectomy and postoperative lavage
• Video-assisted retroperitoneal debridement (VARD)
• Endoscopic transgastric necrosectomy for limited necrosis

Conventional Open Surgical Necrosectomy

Surgical necrosectomy is performed after laparotomy and opening of the omental bursa through the gastrocolic ligament using blunt dissection without sharp instruments.

Since recurrent intra-abdominal sepsis after one-time necrosectomy is a potential problem, different concepts have been developed for the removal of postoperatively remaining necrotic tissue and exudate.

Four methods are known:

• Open packing
• Planned repeated relaparotomies (staged lavage)
• Closed packing
• Closed continuous lavage

Open Packing and Planned Relaparotomy

In cases of massive fluid retention or development of abdominal compartment syndrome in early disease stages. The open abdomen can best be managed with a vacuum dressing.

A primary abdominal wall closure is generally aimed for.

Open packing and planned relaparotomy share the necessity for multiple repetitions of necrosectomy and lavage until treatment completion, thus causing high follow-up morbidity. Repeated necrosectomies, typically required 5 to 10 times, correlate with more frequent intra-abdominal complications including pancreatic fistulas (approximately 25–50%) and bleeding (approximately 20–45%), as well as increased systemic complications. Therefore, both surgical methods are only applied when surgical intervention is necessary in an early phase of acute pancreatitis, i.e., at a time when the necrosis areas are not yet fully demarcated and further surgeries are necessary anyway.

Closed Packing and Closed Continuous Lavage

In closed packing, Penrose drains are introduced into the abscess cavity and left in place for at least 7 days.

In continuous lavage, closed drains are placed in the pancreatic bed. Postoperative lavage begins with a flushing volume of about 10–20 liters per day, which is slowly reduced under infection value control.

Postoperative continuous lavage and closed packing are two surgical methods that allow the postoperative removal of necrotic parts and exudate without reoperation. This can avoid relaparotomy in most cases, and surgical treatment can be completed with a single procedure in about 70–80% of cases. While this does not reduce mortality, it does reduce postoperative morbidity, particularly regarding fistulas (approximately 15–30%) and bleeding (approximately 5–15%) and scar hernias.

In our clinic, we prefer closed continuous lavage. This prevents relaparotomy in the majority of cases. This approach is now the most commonly used worldwide among all surgical procedures.

Minimally Invasive Techniques

Today, in addition to the open surgical technique, various minimally invasive techniques including surgery, endoscopy, and interventional radiology are available.

The retroperitoneoscopic procedure in various variants is the minimally invasive surgical procedure of choice.

Retroperitoneoscopic necrosectomy is part of a step-up approach in the sense of an escalation therapy scheme. In this scheme, if infected necrosis is detected in a septic patient, an interventional drain is placed in the infection focus, and only if clinical stabilization is lacking in the following days is a minimally invasive necrosectomy performed. The inserted drain serves as a guide for the necrosectomy.

Depending on the technique variant, the marked access is then dilated/incised, and necrosectomy is performed video-assisted using a cystoscope, nephroscope, mediastinoscope ("minimal access retroperitoneal pancreatic necrosectomy", MARPN; "video-assisted retroperitoneal debridement", VARD), or also with the help of an endoscope.

If two accesses are created, postoperative continuous lavage with high flushing volume can be performed. The endoscope offers the advantage of flexible direction change, allowing even far retrocolic necrosis parts to be removed without additional accesses.

Comparison of Open and Minimally Invasive Surgical Techniques

It is assumed that selection occurs as to which procedure the respective patient is subjected to.

In contrast to conventional surgical procedures, several minimally invasive interventions are usually necessary until sepsis is controlled, and patients generally remain longer in the intensive care monitoring area and in the hospital.

In contrast to minimally invasive retroperitoneoscopic techniques, the open conventional surgical technique can also be used in emergencies, e.g., in case of suspected bowel ischemia or bleeding, as well as when a stoma or cholecystectomy is necessary.

Endoscopic Transgastric Necrosectomy

Endoscopic necrosectomy is an alternative to the methods already mentioned. Since areas in the pancreatic head are easier to reach via endoscopic technique than percutaneously, while left-sided areas are better accessible percutaneously, a combination of techniques will certainly be sensible in the future. Potential advantages of the transgastric approach are

• painlessness and
• avoidance of cutaneous fistulas.

Disadvantages may include

• the obligatory secondary contamination of the necrosis with intestinal flora,
• the lack of possibility for continuous postoperative lavage, and
• the rapid closure of the access (keeping the access open by inserting plastic stents or a special metal stent (hot-Axios-stent, beware of erosion bleeding after 2 weeks!).

Cholecystectomy

In biliary pancreatitis, the gallbladder should be removed as the source of the triggering concrements.

In the case of a mild course with conservative therapy and healing, this procedure can then be performed electively, usually also laparoscopically. Cholecystectomy should be performed during the first hospital stay – directly after the resolved pancreatitis – as this is possible without increased morbidity and reduces the risk of a recurrent pancreatitis episode in the interval.

In the case of severe pancreatitis requiring laparotomy, preoperative ERCP with papillotomy and possibly stent placement should definitely have been performed in biliary genesis of acute pancreatitis.

• Not for sterile necrosis!
• Avoid the procedure within the first 2 weeks after symptom onset
• Timing: better late than early: preferably 3-6 weeks after symptom onset

The diagnosis is made clinically through abdominal pain accompanied by an increase in amylase or lipase to at least three times the normal level.

Imaging techniques are initially secondary!

Symptoms: often unilateral or bilateral radiating flank pain and a still compressible but diffusely tender abdominal finding, accompanied by nausea and vomiting.

The assessment of the disease course in patients with acute pancreatitis is often difficult. Upon hospital admission, the severity of the disease course can only be assessed very unreliably through clinical examination.

There are various scoring systems for assessing and predicting the severity of the disease course, including:

• Ranson score
• Glasgow score
• APACHE-II score.

However, scoring systems are only conditionally suitable for assessing a patient's risk for a severe disease course. Moreover, due to their complexity, they are rarely used in clinical practice.

Many different laboratory chemical markers have been investigated as specific and reliable predictors of severe disease courses. However, CRP remains the best-evaluated parameter and is considered a reliable predictor of pancreatic necrosis from the third day of illness. The cut-off value for a severe disease course is a CRP over 150 mg/dl.

Since the majority of fatal courses are caused by infection of pancreatic necroses, detecting the infection is particularly important. However, there is still no laboratory parameter that reliably predicts the infection of pancreatic necrosis. Procalcitonin is a marker that can provide indications of a severe disease course within the first 2 days but loses sensitivity and specificity as the course progresses.

Clinical signs of severe acute pancreatitis: Grey-Turner sign or Cullen sign:

• In this case, bluish-greenish spots appear in the flank or navel area. They are caused by edema of the subcutis with local bleeding from small vessels, also referred to as ecchymoses, caused by autodigestion of blood vessels by pancreatic enzymes or by bleeding in the retroperitoneum.
• Ecchymoses below the inguinal ligament (so-called Fox sign) are very rare.

Ultrasound Diagnostics

Basic diagnostics include abdominal sonography to assess the following situations:

• free fluid
• Status of the bile ducts and gallbladder
  • Stones?
  • Bile duct dilation?
  • Inflammation?
• Pancreas, if visible
  • Edema?
  • Calcifications?
  • Free fluid?

X-ray Diagnostics

• Plain abdominal X-ray for differential diagnostic exclusion of perforation (free air) and to assess any accompanying intestinal paralysis (mirror formation).
• Depending on the patient's clinical condition, a chest X-ray should be taken to assess the pulmonary status, particularly for accompanying pleural effusions.

Contrast-Enhanced CT

• Contrast-enhanced CT is now the gold standard for diagnosing pancreatic necrosis and thus for identifying locally complicated pancreatitis.
• Contrast-enhanced CT as extended basic diagnostics is often performed upon patient admission, also depending on the quality of the sonography.
• Since necrosis is only fully developed after 4–5 days, follow-up should be performed to properly assess the extent of the necroses.
• Detection of a superinfection of pancreatic necroses is hardly possible with CT alone, as gas inclusions indicating bacterial infection are rare. Here, fine needle aspiration of necrotic material for microbiological processing must be performed.

Endoscopic Retrograde Cholangiopancreatography (ERCP)

• In mild pancreatitis: not necessary
• In severe pancreatitis: controversial
• If persistent obstruction of the bile ducts: Yes, as soon as possible!

IMC (Intermediate Care)

The goal of basic therapy is to avoid secondary complications of acute pancreatitis such as pulmonary, cardio-circulatory, renal, and metabolic decompensations. Therapeutic intervention is only possible through early detection and treatment of complicated courses.

The basis for reducing the high mortality in the early phase of acute pancreatitis is the immediate initiation of symptomatic intensive care standard therapy.

Risk factors for a severe course:

• High BMI
• Cardiopulmonary pre-existing conditions

Primary and early IMC due to volume requirement and monitoring:

• Pulse oximetry,
• Hematocrit
• Renal retention parameters
• Urine output

Volume substitution

In the early phase of acute pancreatitis, several factors lead to the development of cardio-circulatory decompensation:

• especially the shift of several liters of fluid from intravascular to the "third space",
• electrolyte shift,
• the influx of toxic and vasoactive substances.

To compensate for intravascular volume, central venous pressure, and systemic blood pressure, generous volume substitution (often 300–500 ml/h) is necessary.

Antibiotic therapy

The infection of pancreatic necrosis in the second phase of the disease is the main risk factor for sepsis and multi-organ failure and is associated with high mortality. Prophylactic antibiotic therapy in severe necrotizing pancreatitis aims to reduce the occurrence of infections and septic disease courses, the rate of necessary surgeries, and also mortality.

However, the study situation is controversial:

In the guidelines for the treatment of acute pancreatitis in the United Kingdom, the general recommendation for antibiotic prophylaxis was omitted due to a published multicenter double-blind study. The study could not demonstrate the effectiveness of antibiotic prophylaxis.

Considering all available data, prophylactic antibiotic administration is still recommended for patients with necrotizing forms, especially if more than 50% of the organ is affected or in early organ failure.

Carbapenems are currently considered the antibiotics of choice due to their spectrum of activity and penetration into pancreatic tissue.

Anti-fungal prophylaxis is not recommended.

Intra-arterial application or selective bowel decontamination is being examined in studies.

Analgesia

Adequate analgesia is an important pillar of therapy and has a positive effect on patient outcomes.

Potent opioid analgesics are used, such as buprenorphine, which can be administered sublingually (e.g., 4 × 200–400 µg/d) or intravenously (e.g., 4 × 300 µg/d as a short infusion). Pethidine and piritramide are also suitable as highly potent analgesics, possibly in combination with a peripherally acting analgesic such as metamizole.

In rare cases of failure of intravenous medication pain therapy, a thoracic epidural catheter is an alternative.

The side effect of increased tone of the Sphincter of Oddi with consequent worsening of the course of pancreatitis does not seem to be significant with modern opioid analgesics.

Ventilation therapy

If oxygen saturation drops, oxygen should be administered, and if necessary, intubation and controlled ventilation should be performed. Under no circumstances should adequate fluid substitution be interrupted due to impending respiratory insufficiency.

Oliguria in the first 48 hours after the onset of the disease is associated with a high complication rate of acute pancreatitis in most cases. Nephrotoxic medications should be avoided.

Stress ulcer prophylaxis

In severe pancreatitis, acid blockade is indicated for stress ulcer prophylaxis. Controlled studies on the benefit of stress ulcer prophylaxis are pending, but prophylaxis is generally recommended. Here, intravenous administration of proton pump inhibitors (PPI, e.g., 40–80 mg/d pantoprazole) is preferred.

Enteral nutrition

In recent years, several studies have indicated that enteral nutrition via a jejunal tube in severe courses of acute pancreatitis may have a positive effect on the course of pancreatitis. Early enteral nutrition seems to maintain mucosal integrity, thereby preventing bacterial translocation and being superior to parenteral nutrition. However, enteral nutrition depends on the extent of the subileus and is not feasible in every case. The recommendation for exclusively parenteral nutrition in the early phase of acute pancreatitis is no longer tenable.

A primary nasojejunal tube is favored, especially due to the almost invariably present gastric paralysis in severe acute pancreatitis. This also results in the exclusion of duodenal passage and thus a negative stimulus on the pancreas.

Since patients are already threatened by general complications such as thromboembolism, pneumonia, and bleeding due to the preoperative septic condition and often have undergone long-term intensive medical treatment, one should focus on the urgency of the surgical procedure in addition to general complications such as

• Injury to adjacent structures (intestine, vessels, nerves, other organs)
• Extension of the surgery at the discretion of the surgeon
• Subsequent interventions

and inform about specific complications:

• Induction of bleeding with possible transfusions of donor blood
• Resection of functional tissue with subsequent exocrine and endocrine pancreatic insufficiency
• Pancreatic fistula
• Persistent sepsis
• Late abscesses
• Gastrointestinal fistulas
• Incisional hernia
• Gastric outlet obstruction
• Bile duct strictures
• Pseudocysts