Use of Patient-Controlled Analgesia in Acute Pancreatitis
Use of Patient-Controlled Analgesia in Acute Pancreatitis
Acute pancreatitis (AP) represents a critical health concern nationwide, with estimated
 274,000 admissions annually and at a cost of 2.6 billion dollars. Current treatment
 strategies for AP are limited to supportive care with fluid resuscitation, analgesia,
 nutrition and prevention of end organ damage. Abdominal pain is often the predominant symptom
 in patients with AP and is treated with analgesics. As there is currently no disease-specific
 medical treatment to change the natural history of pancreatitis, pain control remains central
 to the treatment of AP. Among the analgesics, opioids have been shown to be provide safe and
 effective pain control in patients with AP. Current literature shows that there is no
 difference in the risk of pancreatitis complications or clinically serious adverse events
 between opioids and other analgesia options. Among hospitalized AP patients, adequate pain
 control often requires the use of intravenous (IV) opiates in the first 24-48 hours, which
 can later be transitioned to oral (PO) opioids. While there are various methods of delivering
 opioid medications such as IV, PO, and transdermal to name a few, IV opioids are commonly
 administered, either on a scheduled and/or on an as needed (PRN) basis as directed by the
 attending physician. In contrast to the conventional, method of physician directed IV opioid
 delivery, patient-controlled analgesia (PCA) is a form of IV opioid medication delivery in
 which the patient can rapidly titrate the opioid dose to manage variable levels of pain. This
 modality of opioid administration is often preferred by patients and has been widely used in
 postsurgical and obstetric patients to effectively treat their pain. PCA allows for faster
 intervention on pain limiting time to treatment and peak pain levels and has also been shown
 to decrease total opioid dose. However, there is limited evidence in published literature
 assessing the feasibility of using PCA to treat the pain of AP or comparing its efficacy and
 safety profile compared to the more traditional physician directed analgesia. One
 retrospective study has shown that use of PCA was surprisingly associated with longer
 hospital stays and higher rates of outpatient opioid use when compared to routine
 physician-directed analgesia (PDA), however there are no prospective trials to study this
 comparison. Hence, in this study, the investigators will compare the effects of using PCA
 among patients with AP to that of conventional PDA.
-  Investigators will identify patients with AP based on the 2012 revised Atlanta criteria
 for diagnosis, i.e., AP is diagnosed if 2 out of the following 3 criteria are met:

 -  Acute onset of persistent, severe, epigastric pain often radiating to the back,

 -  Elevation in serum lipase or amylase to three times or greater than the upper limit of
 normal,

 -  Characteristic findings of acute pancreatitis on imaging (contrast-enhanced computed
 tomography [CT], magnetic resonance imaging [MRI], or transabdominal ultrasonography).

 -  Patients will be recruited for participation in this study while they are hospitalized
 with AP at Beth Israel Deaconess Medical Center. Once the patient has been transferred
 from the emergency department to the hospital floor, we will identify and recruit them
 for participation in our study.

 -  After obtaining informed consent from the patient, the patient will be enrolled by
 simple randomization to either the PCA or the PDA arm of the study. The research staff
 will assign patients to either the PCA arm or the PDA arm based on a standard
 randomization. Once, a patient has consented, the research staff will assign them to the
 next sequential study identidication number and corresponding study arm and let the
 attending hospitalist know of the result. The patient will then be enrolled in their
 assigned arm.

 -  The initial protocol for analgesic administration in each arm is as follows:

 -  Recommended algorithm for physician directed analgesia (PDA) arm:

 -  IV Hydromorphone 0.4 mg every 4 hours PRN for pain 4-6

 -  IV hydromorphone 0.6 mg every 2 hours PRN for pain 7-10

 -  Rescue IV hydromorphone 0.4 mg every 2 hours PRN for pain 4-10 = only to be
 given as a 'rescue dose' if patient has persistent pain despite using every 4
 hours PRN IV hydromorphone (breakthrough pain)

 -  Maximum opioid dosing: 1 mg per hour and 3 mg of IV hydromorphone per 4 hours

 -  If patient has received more than 2 rescue doses for breakthrough pain in 12
 hours or is in uncontrolled pain: Hospitalist's recommended step-up orders: IV
 hydromorphone 0.8 mg every 4 hours PRN 4-6

 -  Recommended algorithm for patient controlled analgesia (PCA) arm:

 -  IV Hydromorphone 0.1 mg every 10 minutes

 -  Rescue IV hydromorphone 0.4 mg every 2 houra PRN for pain 4-6, hydromorphone
 0.6 mg every 2 hours PRN for pain 7-10 = only to be given as a 'rescue' dose
 for if patient has persistent pain despite using PCA (breakthrough pain)

 -  Maximum opioid dosing: 1 mg per hour and 3 mg of IV hydromorphone per 4 hours

 -  If patient has received more than 2 rescue doses for breakthrough pain in 12
 hours or is in uncontrolled pain: Hospitalist's recommended step-up orders: IV
 hydromorphone 0.2 mg every 10 minutes

 -  Recommended for all patients:

 -  PO Acetaminophen 1000 mg every 8 hours scheduled

 -  IV Naloxone 40-80 mcg PRN for respiratory depression (RR<10) or significant
 somnolence

 -  PO Benadryl 25mg every 4 hours PRN moderate to severe pruritis

 -  Recommended algorithm for transition to oral:

 -  PO Oxycodone 5mg every 4 hours PRN for pain 4-6

 -  PO Oxycodone 10mg every 4 hours PRN for pain 7-10

 -  Rescue PO Oxycodone 5mg every 2 hours PRN for pain 4-10 = only to be given as
 a 'rescue dose' if patient has persistent pain despite using every 4 hours PO
 oxycodone (breakthrough pain)

 -  Dosing and frequencies of medications in the above algorithms are recommendations. The
 recommended doses are not required for maintenance in the study and we anticipate that
 they may change given patient characteristics and variable response to medication, the
 rapidly evolving nature of acute pancreatitis, and hospitalist preferences. However, the
 mode of IV opioid administration (PDA vs PCA) should remain as assigned until transition
 to PO opioid.

 -  Each patient will be closely monitored for adverse events related to opioid
 administration to include cardiorespiratory decompensation, hemodynamic instability,
 nausea, vomiting, confusion, altered mental status, headache, drowsiness, etc. This
 monitoring will include continuous pulse oximetry in addition to vital sign measurement
 every 4 hours.

 -  The efficacy of each treatment arm to adequately control the patient's pain will be
 assessed with scheduled use of the Numeric Rating Scale (NRS) every 4 hours by the
 nursing staff. Pain rating on the NRS will be documented by the nursing staff after each
 assessment. In an NRS, patients are asked to circle the number between 0 and 10 that
 fits best to their pain intensity. Zero usually represents 'no pain at all' whereas 10
 represents 'the worst pain ever possible'.

 -  Likert scale of 1 to 10 (1 = Very poor, 10= excellent) will be used to grade overall
 patient satisfaction with pain control.

 -  Once each patient's pain is well controlled on IV opioid administration (as determined
 by the attending physician) and they can tolerate intake by mouth, transition from IV to
 PO opioid medication can be made in each arm by the attending physician. If the patient
 is unable to tolerate either the PDA or the PCA arm for any reason and requires
 switching over to the other arm as part of his/her clinical care, they will be withdrawn
 from the study and their data will be excluded while analyzing the results. AP has a
 variable course and may require IV opioids after transition to PO opioids. The modality
 of IV opioid administration will revert to the assigned treatment arm.

 -  Other aspects of each patient's routine clinical care will continue as per the attending
 physician under whom the patient is admitted regardless of treatment arm status (PDA vs
 PCA).

 -  At the end of their hospital stay, investigators will document study outcomes.

 -  Investigators expect to enroll patients over a 36-month period from the start date of
 the study. Based on this, investigators expect patient enrollment to end by 4/30/2024.
 Investigators will plan to perform data analysis at two points: 1. Interim data analysis
 at a predetermined point in the study (mid-point of study), and 2. At the end of the
 study once patient enrollment has been completed.
Inclusion Criteria:

 -  Diagnosis of acute pancreatitis confirmed by revised Atlanta criteria

 -  Admitted to the medical floor within 48 hours of emergency department arrival at Beth
 Israel Deaconess Medical Center (BIDMC) in Boston, Massachusetts.

 -  Age 18-65

 Exclusion Criteria:

 -  Active illicit drug use

 -  Discharged from the emergency department

 -  Direct admission to ICU from emergency department

 -  Known allergy to opioid medications

 -  Age <18 or >65

 -  Known chronic pain syndrome or concurrent other medical condition with chronic pain

 -  Active encephalopathy/confusion/delirium/psychiatric illness or any other condition
 that limits capacity

 -  Known chronic opioid use

 -  Renal insufficiency (baseline Creatinine of >2 and/or acute kidney injury with
 Creatinine>3 on admission)

 -  Known allergy to acetaminophen or hepatic dysfunction otherwise limiting acetaminophen
 use