Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician. Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure. This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.
Tag Archives: pancreatitis
More Data Supporting Lactated Ringers for Acute Pancreatitis
A Lee et al. Gastroenterol 2021; 160: 955-957. Lactated Ringers vs Normal Saline Resuscitation for Mild Acute Pancreatitis: A Randomized Trial
PK Garg et al. Gastroenterol 2021; 160: 655-59. Full text (editorial) Optimum Fluid Therapy in Acute Pancreatitis Needs an Alchemist
Key findings from this double-blind randomized controlled trial (n=121):
- ICU admissions were 9.8% in LR group compared with 25% of NS group (RR 0.4, CI 0.2-0.9)
- Quicker discharge with 44% at 72 hrs in LR group compared with 28% in NS group
- Median length of stay was 3.5 days (LR group) compared with 4.6 days (NS group)
Critique of study from editorial: “The strengths of their study include a well-designed protocol, reasonable sample size and inclusion of patients within 8 hours of diagnosis; thus, fluids were administered during the critical period when there is a window of opportunity to restore the intravascular volume and maintain adequate tissue perfusion. However, the study included patients with mild pancreatitis. Another issue is that the benefit shown was for secondary outcomes and, thus, these results should be taken as exploratory and hypothesis generating.”
My take: For now, lactated ringer’s is the fluid of choice in individuals with acute pancreatitis.
Related blog posts:
- LR in Pediatric Pancreatitis, NASPGHAN18 Abstract (Peter Farrell)
- Acute Pancreatitis: NASPGHAN Clinical Report.
- Acute Pancreatitis Review (2016)
- For the pediatric pancreatologists
- Pancreatitis Update (part 1) | gutsandgrowth 2017
- Pancreatitis Update (part 2) 2017
- Changing Practice Patterns with Pediatric Pancreatitis | gutsandgrowth
- Why an ERCP Study Matters to Pediatric Care | gutsandgrowth This post explains why LR may be best.
Reducing Inappropriate Proton Pump Inhibitor Usage & U.S. Children with COVID-19
D Lin et atl. Clin Gastroenterol Hepatol 2020; 18: 763-6. In a retrospective chart review, the authors examined pharmacy data from patients in the Harris Health System (Harris county -Houston, TX) which had more than 1.9 million outpatient clinic visits in 2017.
In January 2018, multiple efforts were made to try to reduce inappropriate proton pump inhibitor (PPI) usage. This included grand rounds and system-wide emails to providers. In addition, a suggested tapering algorithm (order in EPIC) was given to reduce the likelihood of rebound acid hypersecretion which could undermine the goal of stopping PPI.
- Taper: When ready to taper, start with “a PPI every other day for 2 weeks, followed by a PPI every 4 days for 2 additional weeks before discontinuation.”
- De-escalation: Before educational intervention, in 2017, there were 66,261 unique PPI prescriptions. After educational intervention, in 2018, there were 55,322 unique PPI prescriptions (16.5% decrease). This equates to ~800,000 fewer capsules or pills dispensed in 1 calendar year
- The most “important driver” for de-escalation was the initiation of the discussion by the ambulatory primary care provider
- The authors recommend clinic followup within a month after starting de-escalation and gastroenterology evaluation for patients with severe symptoms or those refractory to PPI treatment
My take: This study indicates that 1 in 6 PPI users were able to de-escalate off treatment. Physician initiative is crucial to improve appropriate medication use.
Related blog posts:
- Deconstructing PPI-Associated Risks with Nearly 8 Billion Pieces of Data
- PPIs: Good News on Safety Large randomized double-blind study of pantoprazole: “we found that pantoprazole is not associated with any adverse event when used for 3 years, with the possible exception of an increased risk of enteric infections.”
- PPIs: Good News on Safety (Part 2, 2019)
- Favorable “Break”through Data for PPIs and Bone Density
- Which PPIs are most potent?
- PPIs: Dissecting the Evidence
- The Prosecution Rests…PPIs on Trial
- No Effect of Proton Pump Inhibitors and Irritability on Crying in Infants
- Two for the PPI Team
- Proton Pump Inhibitors Webinar | gutsandgrowth
Recent study from JAMA Pediatrics (5/11/20) -Full text: Characteristics and Outcomes of Children With Coronavirus Disease 2019 (COVID-19) Infection Admitted to US and Canadian Pediatric Intensive Care Units
Of the 48 children with COVID-19 admitted to participating PICUs (14 hospitals)… Forty patients (83%) had significant preexisting comorbidities; 35 (73%) presented with respiratory symptoms and 18 (38%) required invasive ventilation….At the completion of the follow-up period, 2 patients (4%) had died and 15 (31%) were still hospitalized, with 3 still requiring ventilatory support and 1 receiving extracorporeal membrane oxygenation. The median (range) PICU and hospital lengths of stay for those who had been discharged were 5 (3-9) days and 7 (4-13) days, respectively.
NY Times Summary of Study: Details of U.S. Children Severely Affected by Coronavirus
Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician. Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure. This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition
NASPGHAN Postgraduate Course 2017 (Part 3): Biliary Atresia, NAFLD, SMOFlipid, Pancreatic Pain
This blog entry has abbreviated/summarized these presentations. Though not intentional, some important material is likely to have been omitted; in addition, transcription errors are possible as well.
Here is a link to postgraduate course syllabus: NASPGHAN PG Syllabus – 2017
Biliary Atresia: Update on diagnostic and prognostic biomarkers and therapeutic interventions
Cara Mack Children’s Hospital of Colorado
- 84% of biliary atresia is isolated; 16% are syndromic with other defects
- Direct bilirubin is (mildly) elevated at birth in patients with biliary atresia
- Total bilirubin 3 months after Kasai predicts outcome. If <2 mg/dL, then unlikely to need a transplant in the first 2 years of life.
- Reviewed biomarkers including Th1, Autotaxin, IL-8
- Nutritional support. Better nutrition improves outcomes after liver transplantation.
- Fat soluble vitamin supplementation
- Cholangitis prevention. Some studies have shown that prophylactic antibiotics may reduce incidence of cholangitis.
- No therapeutic interventions that delay progression of this disease
Diagnosis and Management of Pediatric NAFLD 2017
Stavra Xanthokos Cincinnati Children’s Hospital Medical Center
- NAFLD is #2 cause of liver transplantation in adults and on its way to becoming #1
- ALT is still the best screening tool; NASPGHAN guidelines recommends screening overweight/obese children 9-11 years of age
- Ultrasound has poor sensitivity and specificity for NAFLD; it is helpful for detecting gallbladder disease
- Bariatric surgery has been effective for NAFLD
SMOFlipid and the Pediatric Patient
Peter Wales Hospital for Sick Children (Toronto)
Slides are not available in syllabus
- Improving outcomes noted in the intestinal failure population
- Dr. Wales reviewed proposed improvements with Omega-3 lipids -less cholestasis, less hepatitis, and less fibrosis
- Compared improvements with lipid minimization (1 g/kg/day) compared to newer agents: omegaven and SMOFlipid. Additional studies are needed due to limitations of previous studies
- Discussed SMOFlipid vs. Intralipid trial at 5 centers in Canada. N=24.
- At SickKids: SMOFlipid for all preterms at admission & for term infants after 2 weeks of PN. Dosing 2-2.5 g/kg & now accounts for 85% of lipid usage at institution
- None of the lipid products were designed for preterm infants. Intralipid has a pediatric indication and other products are used off label
- Lipid restriction probably affects brain size/development; thus, a lipid agent that allows for higher doses likely will be beneficial for developmental outcomes. The retina can be used as a biomarker of the brain affects of lipids.
Painful Chronic Pancreatitis: Management/therapeutic interventions
Vikesh Singh Johns Hopkins University School of Medicine
Slides are not available in syllabus
FDA Warning on Eluxadoline (Viberzi)
Briefly noted: The FDA has issued a safety warning for patients with irritable bowel syndrome who have had their gallbladder removed.
FDA Warns of Increased Risk of Serious Pancreatitis with irritable bowel drug eluxadoline (Viberzi) in patients without a gallbladder
Viberzi is a prescription medicine used to treat irritable bowel syndrome in adults when the main symptom is diarrhea (IBS-D)…From May 2015, when Viberzi was first approved, through February 2017, FDA received 120 reports of serious cases of pancreatitis or death.* Among the 68 patients who reported their gallbladder status, 56 of them did not have a gallbladder and received the currently recommended dosage of Viberzi. Seventy-six patients were hospitalized, of which two patients died.
My take: Now that this warning has been issued, there may be additional cases identified. While this medication is mainly used in adults, pediatric gastroenterologists need to be aware of this risk in counseling potential patients.
Related blog posts:
- Eluxadoline for Irritable Bowel Syndrome with Diarrhea
- FDA Approves Rifaximin and Eluxadoline for IBS-D | gutsandgrowth
Top Posts 2016
The following posts are the ones that I think are most useful from 2016.
- Is Intestinal Function in Children with Autism Different? | gutsandgrowth
- How Likely is Reflux in Infants with “Reflux-like … – gutsandgrowth
- Is a Gluten-Free Diet a Heathy Diet for Those without Celiac Disease
- Ultra-Short Celiac Disease | gutsandgrowth
- Adrenal Insufficiency due to Fluticasone in … – gutsandgrowth
- Adverse Events Following Pediatric Endoscopy … – gutsandgrowth
- Don’t Skip this Article -Rome IV Summary | gutsandgrowth
- Rome IV -Pediatric Changes | gutsandgrowth
- Bad News Bili | gutsandgrowth
- Changing Approach to Neonatal Acute Liver Failure | gutsandgrowth
- Biliatresone- Early Preview of Basic Science Lecture
- Intellectual Disability in Pediatric Liver Transplantation | gutsandgrowth
- Why Some Kids Are Short
- Topamax and Amitriptyline Did Not Work for Pediatric Migraines
- What to Make of a Low Alkaline Phosphatase | gutsandgrowth
- CDC Guideline for Prescribing Opioids for Chronic Pain | gutsandgrowth
- ERAS -Enhanced Recovery After Surgery | gutsandgrowth
- Patient assistance for lab testing
- John Oliver and Understanding Scientific Studies
- Expert Review: GMOs are Safe
- NY Times: “Never Diet Again” | gutsandgrowth
- Landmark Study: Ustekinumab
- Lower Fiber Intake May Increase Risk of Crohn’s Flare | gutsandgrowth
- How helpful are serologies in pediatric inflammatory … – gutsandgrowth
- 4 Points for C diff in Inflammatory Bowel Disease | gutsandgrowth
- What to Make of Post-op Treatment for Crohn’s Disease | gutsandgrowth
- CCFA Conference Notes 2016 (part 2) -Pediatric … – gutsandgrowth
- Detrimental Effect of Early Parenteral Nutrition in … – gutsandgrowth
- Latest Obesity Data Discouraging | gutsandgrowth
- Changing Practice Patterns with Pediatric Pancreatitis | gutsandgrowth
- Parent Perspective, Pediatric Nutritionist and Traci Nagy | gutsandgrowth
- The “EAT” Study | gutsandgrowth
Complex Family of CFTR-Associated Disorders
While most clinicians are familiar with cystic fibrosis (CF), much fewer are familiar with a group of disorders related to the cystic fibrosis transmembrane conductance regulator (CFTR) that do not meet the criteria for cystic fibrosis. A summary of these disorders is provided in a recent editorial (Levy H, Farrell PM. J Pediatrics 2015; 166: 1337-40). In addition, the editorial provides insight into a related study: Groves T et al.. J Pediatrics 2015; 166: 1469-74.
The editorialists note that new disorders have been created due to newborn screening and due to the use of CF mutation analysis. New disorders:
- CRMS -CFTR-related metabolic syndrome. CRMS describes infants with elevated immunoreactive trypsinogen and inconclusive sweat testing and DNA results. Inconclusive sweat testing includes sweat tests 30-59 mmol/L if age <6 months or 40-59 mmol/L if >6 months on at least 2 occasions. DNA testing is inconclusive if there are fewer than 2 CF disease-related mutations identified. DNA testing is also considered inconclusive if there are 2 CFTR mutations but sweat testing is normal.
- CFTR-RD -CFTR related disease. CFTR-RD describes symptomatic individuals beyond infancy who have sweat testing <60 mmol/L and up to 2 CFTR mutations, at least one of which is not clearly categorized as a CF-causing mutation. Thus, these individuals do not fulfill criteria for CF but could have congenital bilateral absence of vas deferens, acute recurrent or chronic pancreatitis, or disseminated bronchiectasis.
- Delayed CF -Delayed CF describes patients eventually diagnosed with CF who had initially intermediate sweat chloride values. Over time, their condition evolves to fulfill the criteria for CF. In the retrospective study by Groves et al, 14 of 29 (48%) evolved to a diagnosis of CF. These patients with delayed CF had less pancreatic insufficiency (OR 0.06), milder obstructive lung disease, less colonization with Pseudomonas aeruginosa (OR 0.04), and overall disease severity as measured by Shwachman scores at 2 years.
- Nutritional outcomes were improved at 2 years in this Delayed CF cohort in comparison to 28 matched patients diagnosed with CF in the newborn period, but did not persist to later ages.
The editorial notes that nearly 20% of patients with CF are being enrolled in the CF foundation patient registry without sweat chloride testing results. They do not favor this approach because the diagnosis of CF requires proof of CFTR dysfunction, not simply CF DNA mutations.
Take-home message: Patients who do not meet the criteria for CF but who have intermediate sweat testing or abnormal CF DNA mutations need to be followed. Some will fulfill the criteria with time and others may develop other clinical problems even without having CF.
Why an ERCP Study Matters to Pediatric Care
While there are pediatric patients who undergo endoscopic retrograde cholangiopancreatography (ERCP), this is a relatively infrequent occurrence. Nevertheless, a recent study has a couple useful clinical pearls that may have broader application.
- Clin Gastroenterol Hepatol 2014; 12: 303-07.
- Clin Gastroenterol Hepatol 2014; 12: 308-10 Associated editorial
- Gastroenterol 2014; 146: 581-82. Associated summary
- Aggressive hydration may prevent post-ERCP pancreatitis. In the study, the treatment group received an average of 3290 mL over the 9-hour period compared with 945 mL in the standard infusion group.
- Implication: The speculation from the study and the editorials is that improved pancreatic perfusion will result in better oxygenation and reduce the likelihood of pancreatitis. In the 2nd reference, the author states that his practice is to administer “at least 3 L of crystalloid in recovery to young, healthy patients who have undergone high-risk ERCP and an additional 3 to 5 L within the first 12 hospital hours to those admitted with postprocedure pain”
- The best fluid (for post-ERCP and acute pancreatitis) may be lactated Ringer’s (LR).
- Implication: The lactate in LR may help reduce pancreatitis by avoiding acidosis which could promote zymogen activation and pancreatic inflammation. A previous small trial (n=40) of acute pancreatitits from any cause showed lesser degrees of systemic inflammatory response with LR in compared with normal saline (Clin Gastroenterol Hepatol 2011; 9: 710-17e1).
- This study adds aggressive IVFs as another intervention to prevent ERCP. Rectal indomethacin and prophylactic stent placement (in high-risk patients) are other accepted treatments.
This pilot study randomly assigned 39 patients to aggressive hydration and 23 to standard hydration; all patients were inpatients who were not at risk for fluid overload. The aggressive group received 3 mL/kg/h during the procedure, a 20 mL/kg bolus after the procedure, and then continued on 3 mL/kg/hr for 8 hours. In contrast, the standard group received LR at 1.5 mL/kg/h during and for 8 hours afterwards.
Demographics: The average age was 43 years in the aggressive hydration group and 45 years in the standard group. 78% were hispanic. The ERCP procedures were mostly “average risk.” 74% had ERCP for choledocholithiasis. Only 2 subjects needed precut sphinterotomy (3%).
- No patients in the aggressive hydration group developed acute pancreatitis compared with 4 (17%) in the standard hydration group
- Elevated amylase (23% vs. 39%) and epigastric pain (8% vs 22%) were also less frequent in the aggressive hydration group.
Numerous Limitations: This was a small pilot study with an atypical population; thus, the findings are difficult to generalize. A false-positive (type 1 error) can easily occur due to the small numbers, especially as the standard hydration group had a rate of acute pancreatitis that was about double from previous studies. In addition, this study was not blinded and could have been susceptible to bias. Furthermore, the authors defined acute pancreatitis differently than in previous studies. In this study, the authors required enzyme increases 2 or 8 hours after ERCP with new abdominal pain; in previous studies, the definition of acute pancreatitis relied on enzyme increases for at least 24 hours after the ERCP.
Take-home message for those not doing ERCPs: Think about using lactated ringer’s and aggressive hydration in otherwise-well patients who present with acute pancreatitis.
Related blog entries:
For the pediatric pancreatologists
Pancreatitis is a terrible affliction whether acute, recurrent or chronic. While pediatric patients often have “mild” problems from acute pancreatitis, even in these cases the pain is usually severe and the treatment, which consists mainly of holding feedings and providing pain relief, does not impress anyone.
A few recent references do provide more data on several aspects of pancreatitis.
The first reference, J Pediatr 2013; 162: 788-92, provides data on the rare problem of acute necrotizing pancreatitis in children. This retrospective study encompassing 21 years identified seven children. CT scan showed necrosis of more than 30% and/or more than a 3 cm area in all of these patients. Etiologies included medications (L-asparaginase, Valproate, Minocycline), diabetes (n=1), and gallstones (n=1). No patients needed surgery or died. After discharge, 5 patients had complications which included pseudocysts, diabetes, and pancreatic exocrine insufficiency.
- CT scan (with contrast) is useful in diagnosis and assessment of severity.
- Initial presentation is similar to cases of acute pancreatitis without necrosis. Long-term complications are increased.
The second reference: Gastroenterol 2013; 144; issue 6. The entire issue is devoted to pancreas issues. Pages 1272-81 review acute pancreatitis, pages 1282-91 review chronic pancreatitis, and pages 1292-1302 review genetic risk factors.
Page 1288 provides a suggested management algorithm for chronic pancreatitis:
Medical therapy recommendations include alcohol/smoking cessation, counsel regarding nutrition/vitamin D/calcium, consider analgesics (start with tramadol), consider adjuncts for pain (e.g.. neuron tin, SSRI, SSNRI, TCAs), assess exocrine and endocrine function (elastase and HgbA1C), use steroids if autoimmune pancreatitis.
If medical therapy ineffective, assessment of pancreatic duct is recommended. Based on this information, discussion of endoscopic and surgical treatment is outlined as well.
Related blog entries:
INSPPIRE for pancreatitis
While anyone who follows this blog knows that I like acronyms, I must say that many investigators have taken lessons from Krispy Kreme on spelling. INSPPIRE is named for the International Study Group of Pediatric Pancreatitis: In Search for a Cure. A study from this group reports on definitions of pediatric pancreatitis & surveys current practice (JPGN 2012; 55: 261-65).
The literature regarding acute recurrent pancreatitis and chronic pancreatitis in children is limited. This consortium hopes to change this. As a start, the authors assigned subcommittees to establish definitions, reviewed the literature, and assessed current practice.
- Acute pancreatitis (AP): requires at least 2 of 3 criteria:
- Abdominal pain consistent with AP
- Serum amylase and/or lipase activity at least 3 times ULN
- Imaging findings compatible with AP
- Acute recurrent pancreatitis (ARP): requires at least two episodes of AP along with
Complete resolution of pain (≥ 1-month pain-free interval) OR complete normalization of pancreatic enzyme levels along with resolution of pain (can be shorter interval than 1 month)
- Chronic pancreatitis (CP): requires one of the following:
- Abdominal pain and imaging suggestive of chronic pancreatic damage
- Exocrine pancreatic insufficiency and imaging suggestive of chronic pancreatic damage
- Endocrine pancreatic insufficiency and imaging suggestive of chronic pancreatic damage
- Surgical/histologic specimen consistent with chronic pancreatitis
Typical tests for these three conditions are shown in figure 2 and vary widely. For AP, most respondents (63%) routinely checked liver enzymes, triglycerides, calcium and abdominal ultrasound. For ARP and CP, most respondents (69%) obtained additional imaging modalities (eg. MRCP), genetic testing, and sweat chloride. If ERCP was needed, 88% of practices relied on adult gastroenterology colleagues.
Related blog posts: