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					    Acute pancreatitis


           Mohammad Hossein Somi
          professor of gastroenterology
Liver and Gastrointestinal Disease Research Center
      Tabriz University of Medical Sciences



                                                     1
      INCIDENCE AND
        MORTALITY
 The incidence of acute pancreatitis in
  England, Denmark, and the United States
  varies from 4.8 to 24.2 per 100,000
 In a retrospective study from the
  Netherlands, the observed incidence of
  acute pancreatitis increased by 28%
  between 1985 and 1995, but the mortality
  remained stable due to a decrease in the
  case-fatality rate
                                             2
      INCIDENCE AND
        MORTALITY
 The mortality in the first two week period is
  usually due to systemic inflammatory
  response syndrome and organ failure, while
  after two weeks it is usually due to sepsis
  and its complications
 The frequency of early (<two weeks after
  onset) death has been to reported vary from
  0 to 50 percent of all deaths due to acute
  pancreatitis
                                              3
         INCIDENCE AND
           MORTALITY
   Advances in diagnostic and therapeutic
    interventions have lead to a decrease in
    mortality from acute pancreatitis, especially in
    those with severe, often necrotizing
    pancreatitis
   While the overall mortality in all hospitalized
    patients with acute pancreatitis is
    approximately 10% (range 2 to 22 percent), the
    mortality in the subset with severe acute
    pancreatitis may be as high as 30 percent

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MEDICAL TREATMENT OF
 ACUTE PANCREATITIS




                   10
   Acute pancreatitis can be divided into two
    broad categories
   Edematous or mild acute pancreatitis

   Necrotizing or severe acute pancreatitis
    – A subgroup of patients has early severe acute
      pancreatitis characterized by extended pancreatic
      necrosis with organ failure at admission

                                                          11
       GENERAL PRINCIPLES OF
             THERAPY
   Treatment of acute pancreatitis is aimed at :
   Correcting any underlying predisposing factors
    :
    – Early ERCP in patients with gallstone pancreatitis
      who have obstructive jaundice or biliary sepsis
    – Reversal of hypercalcemia
    – Cessation of possible causative drugs
    – The administration of insulin to the poorly
      controlled diabetic with marked
      hypertriglyceridemia.
   The pancreatic inflammation itself

                                                           12
   Mild pancreatitis is treated for several days
    with supportive care including:
    – Pain control
    – Intravenous fluids
    – NPO


   The majority of patients require no further
    therapy, and recover and eat within three to
    seven days
                                                    13
           Supportive treatment
   In severe pancreatitis, ICU monitoring and support of
    pulmonary, renal, circulatory, and hepatobiliary function
    may minimize systemic sequelae

   These patients need monitoring of vital signs and urine
    output every few hours in the first 24 to 48 hours

   Patients with severe pancreatitis will need ongoing
    monitoring for other complications that might arise


                                                                14
             Fluid resuscitation
   Fluid resuscitation is particularly important because
    patients with necrotizing pancreatitis accumulate vast
    amounts of fluid in the injured pancreatic bed

   Inadequate hydration can lead to hypotension and acute
    tubular necrosis

   Fluid depletion damages pancreatic microcirculation and
    results in pancreatic necrosis


                                                              15
              Fluid resuscitation
   Approximately 250 to 300 cc of intravenous fluids per
    hour are typically required for 48 hours if the cardiac status
    permits

   Adequate fluid replacement can be assessed by
    improvement in vital signs and urine output and reduction
    in hematocrit over 24 hours, particularly if it was high at
    the onset

   In some patients, a low urine output may already reflect the
    development of ATN rather than persistent volume
    depletion

                                                                16
           supplemental oxygen
   Oxygen saturation needs to be assessed routinely and
    supplemental oxygen administered to maintain arterial
    oxygen saturation of greater than 95 percent
    – Blood gas analysis should be done if SaO2 is less than 95 percent
       or if clinical situation demands.



   Prophylaxis against DVT should be considered in
    bedridden patients
    – Intermittent pneumatic compression may be the preferred method
       because of the theoretical risk of precipitating pancreatic
       hemorrhage with anticoagulation


                                                                          17
             Pain management
   Abdominal pain is often the dominant symptom
   Adequate pain control requires the use of intravenous
    opiates, usually in the form of a patient controlled
    analgesia (PCA) pump
   Meperidine has traditionally been favored over morphine
    for analgesia in pancreatitis, probably because human
    studies showed that morphine caused an increase in
    sphincter of Oddi pressure

   Despite these data there is no clinical evidence to suggest
    that morphine can aggravate or cause pancreatitis or
    cholecystitis

                                                                  18
              Pain management
   Repeated doses of meperidine can lead to accumulation of
    the metabolite normeperidine that causes neuromuscular
    irritation and, rarely, seizures

   An alternative is intravenous fentanyl, which use in
    patients who require large doses of meperidine

   As with other opiates, fentanyl can depress respiratory
    function
    – Concurrent use of a calcium channel blocker and a beta-adrenergic
       blocker with fentanyl has resulted in severe hypotension.



                                                                     19
Preventing infection in severe acute
            pancreatitis
   The occurrence of pancreatic infection is a leading cause of
    morbidity and mortality in acute necrotizing pancreatitis

   Approximately one-third of patients with pancreatic
    necrosis develop infected necrosis

   Patients who develop infection tend to have more
    extensive necrosis compared to those in whom the necrotic
    tissue remains sterile


                                                              20
    Preventing infection in severe acute
                pancreatitis
   Although infection can occur early in the course of necrotizing
    pancreatitis, it is more often seen late in the clinical course (after 10
    days).
   In one report, for example, necrotic material obtained at surgery was
    cultured in 114 patients with necrotizing pancreatitis but no abscess
    formation
   Bacterial contamination was present in 24 percent of patients operated
    on within the first seven days and rose to 71 percent in patients
    operated on in the third week
   Identical results were noted in another series in which infection (as
    determined from fluid obtained by CT-guided drainage) developed in
    71 percent of patients with pancreatic necrosis



                                                                            21
    Preventing infection in severe acute
                pancreatitis
   The important organisms causing infection in necrotizing pancreatitis
    are predominantly gut-derived, including Escherichia coli,
    Pseudomonas, Klebsiella, and Enterococcus spp.

   The majority of infections (about 75 percent) are monomicrobial

   Fungal infection and infection with gram-positive organisms are
    uncommon but occur more frequently in the setting of prophylactic
    antibiotic use for severe acute pancreatitis, especially when used for
    more than 10 to 14 days

   Fungal infections occur in approximately 9 percent of necrotizing
    pancreatitis and it is not clear if they are associated with higher
    mortality


                                                                             22
    Preventing infection in severe acute
                pancreatitis
   Three approaches have been taken to decrease bacterial infections in
    acute necrotizing pancreatitis:

     – Enteral feeding to
          Avoid central line related infections
         Maintain gut barrier integrity

         Decrease bacterial translocations

     – Selective decontamination of the gut with nonabsorbable
       antibiotics
     – Prophylactic systemic antibiotics



                                                                           23
    Selective decontamination of
               the gut
   Tthe source of bacterial infections in acute necrotizing pancreatitis is
    the gut
   Thus, reduction of intestinal bacteria through the use of oral-
    nonabsorbable antibiotics could theoretically reduce the risk of
    infection

   This hypothesis was supported in a controlled trial involving 102
    patients with severe acute pancreatitis who were randomly assigned to
    standard treatment or gut decontamination (using a combination of oral
    norfloxacin, colistin, and amphotericin)

   Overall mortality was significantly lower in patients assigned to gut
    decontamination (22 versus 35 percent).

                                                                               24
              Systemic antibiotics
   The role of prophylactic systemic antibiotics in acute pancreatitis is
    unsettled since studies evaluating its benefits and harms have produced
    disparate results

   Initial studies done in the mid-1970s failed to show a benefit, possibly
    because they included patients with mild disease who were at low risk
    for infection and used antibiotics that had poor penetration into the
    pancreas (such as ampicillin).

   In contrast, some more recent studies demonstrated improved
    outcomes associated with the use of prophylactic antibiotics in patients
    with severe necrotizing pancreatitis,



                                                                           25
Complication of AB prophilaxis
   Because of the risk of fungal infections

    – Some authorities advocate the use of prophylactic
      antifungal therapy, an approach that remains to be
      validated

    – Others recommend that prophylactic antibiotics
      should not be used for longer than 7 to 10 days to
      prevent superinfection with gram-positive and
      fungal organisms
                                                           26
     Recommended approach
 After assessment of the patient, a contrast-enhanced CT
  scan is indicated only in patients who are deteriorating or
  have severe pancreatitis determined clinically and by
  APACHE II score.
 A CT scan is not required on the first day unless there are
  other possible diagnoses

 It takes time for pancreatic necrosis to develop, and
  treatment is unlikely to be altered on the basis of CT
  findings on day one


                                                                27
   If there is necrotizing pancreatitis (involving more than approximately
    30 percent of the pancreas), initiate antimicrobial therapy with
    imipenem/meropenem and continue it for at least one week
   Do not routinely recommend prophylactic antifungal therapy with
    fluconazole

   Patients without severe necrotizing pancreatitis are managed
    conservatively with the supportive care

   If at any time the patient becomes unstable from pulmonary,
    cardiovascular, or renal complications, we perform a minimally
    invasive necrosectomy, (endoscopic, or percutaneous radiologic) if
    possible , to remove necrotic debris and pus



                                                                          28
   If there has been no improvement after one week of antibiotics,
    perform a percutaneous CT-guided aspiration

   If there is bacterial infection, consider performing a necrosectomy and
    change the antibiotics according to the culture and sensitivity results

   If, on the other hand, the aspirated material is sterile, continue
    conservative treatment for four to six weeks since most such patients
    do well with medical therapy

   However, if clinical suspicion for infection is high, a repeat aspiration
    may be indicated since a negative FNA does not confidently exclude
    infection



                                                                            29
      Miscellaneous treatments
   A variety of other therapies have been evaluated in the treatment of
    acute pancreatitis.
   Plasma exchange dramatically reduced triglyceride levels and
    improved the outcome in two patients with necrotizing pancreatitis due
    to hypertriglyceridemia

   Intravenous infusion of heparin reduced triglyceride levels and
    improved the outcome in a pregnant patient with severe acute
    pancreatitis due to hypertriglyceridemia and may be an option in such
    cases

   Hypocalcemia (seen in severe cases) can be treated like any other case
    of low calcium with no special recommendation because of acute
    pancreatitis


                                                                         30
                    Nutrition
   Patients with mild pancreatitis can often be
    managed with intravenous hydration alone
    since recovery often occurs rapidly
   In contrast, nutritional support is required in
    patients with severe pancreatitis
   Such patients typically have been fed
    parenterally because they often have an ileus
    and abdominal pain, and because of the
    potential for stimulating the pancreas with
    enteral feeding

                                                      31
                      Nutrition
 Enteral feeding appears safe and feasible in many patients
  with acute severe pancreatitis
 Whenever possible, radiologic or endoscopic placement of
  a jejunal feeding tube beyond the ligament of Treitz and
  enteral feeding should be attempted
 Usually, it is possible to do this within three to five days
  by which time it is possible to make a diagnosis of severe
  pancreatitis and assess for ileus
 use high protein, low fat preparations such as Peptamen.
  Parenteral nutrition should be initiated in patients who do
  not tolerate enteral feeding or in whom nutritional goals
  cannot be reached within two days.
                                                             32
    Initiation of oral feedings
 When to begin oral feedings?
 what to feed?
 How often to feed are questions that arise in
  every patient with acute pancreatitis?
 There have been only a few prospective
  studies:


                                              33
        Initiation of oral feedings
   In mild pancreatitis, oral intake is encouraged early and advanced from
    clear liquid diet to solid food as tolerated

   Recovery generally occurs quickly, making it generally unnecessary to
    initiate supplemental nutrition

   Begin oral feedings by giving 100 to 300 mL of clear liquids every
    four hours for the first 24 hours

   If this diet is tolerated, feedings are advanced gradually over three to
    four days to soft and finally to solid foods



                                                                               34
        Initiation of oral feedings

   All feedings contain greater than 50 percent carbohydrate
    and the total caloric content is gradually increased from 160
    to 640 Kcal per meal
   Oral feeding is frequently not tolerated due to postprandial
    pain, nausea, or vomiting probably related to gastroduodenal
    inflammation and/or extrinsic compression from fluid
    collections leading to GOO

   Such patients can generally tolerate feeding through a jejunal
    tube, which can be placed endoscopically or radiologically

                                                          35
       Initiation of oral feedings
   If the target rate is not achieved within 48 to 72 hours,
    supplemental parenteral nutrition should be provided.

   Jejunal feeding permits earlier discharge from the hospital
    and avoidance of TPN

   A few weeks of jejunal feeding allows for the
    inflammation to subside or the fluid collection to mature
    and be drained, leading to resolution of gastric outlet
    obstruction and resumption of oral feeding


                                                                36
                ACG GUIDELINE
   Risk factors for disease severity that should be noted on admission
     – Older age (>55 years), Obesity (BMI>30 kg/m2), Organ failure at
       admission, and pleural effusion and/or pulmonary infiltrates
          Such patients may require treatment in a highly supervised area

   The two tests that are most helpful at admission in distinguishing mild
    from severe acute pancreatitis are the APACHE-II score and the
    hematocrit.
   The APACHE-II score should be generated during the first three days
    of hospitalization and repeated as needed.
   The hematocrit should be measured on admission, 12 hours after
    admission, and 24 hours after admission to help assess the adequacy of
    fluid resuscitation



                                                                             37
              ACG GUIDELINE
   Pancreatic necrosis and organ failure are the two most
    important markers of severity in acute pancreatitis

   The distinction between interstitial and necrotizing
    pancreatitis can be established after two to three days of
    hospitalization by contrast-enhanced CT scan.

   Supportive care is critical with emphasis on the prevention
    of hypoxemia and the adequacy of fluid resuscitation


                                                                 38
            ACG GUIDELINE
   Prompt transfer to an intensive care unit is
    warranted in patients with sustained organ
    failure
   Transfer to an intensive care unit or possibly a
    step-down care unit should also be considered
    if there are signs that suggest that the
    pancreatitis is severe or is likely to be severe.
   Whenever possible, enteral feeding rather than
    total parenteral nutrition is suggested for
    patients with acute pancreatitis who require
    nutritional support

                                                    39
              ACG GUIDELINE
   The use of prophylactic antibiotics to prevent pancreatic
    infection is not recommended.
   CT-guided percutaneous aspiration with Gram's stain and
    culture is recommended when infected pancreatic necrosis
    is suspected

   The preferred treatment of this problem is surgical
    debridement, but minimally invasive approaches may be
    used in selected cases


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Managment
algorithm for
severe acute
 pancreatitis




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