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.

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Choosing the Right IV Fluids

As noted in previous posts, I tend to favor isotonic IV fluids due to risk of hyponatremia with hypotonic fluids. A new study (below) indicates that some isotonic fluids are associated with an increased risk of electrolyte disturbances. Thanks to Ben Gold for this reference.

In this unblinded, randomized clinical trial with 614 children, participants were randomized to receive commercially available plasmalike isotonic fluid therapy (140 mmol/L of sodium and 5 mmol/L potassium in 5% dextrose) or moderately hypotonic fluid therapy (80 mmol/L sodium and 20 mmol/L potassium in 5% dextrose).

Key findings:

  • Clinically significant electrolyte disorder was more common in children receiving plasmalike isotonic fluid therapy:
    • Hypokalemia developed in 57 patients (19%) and hypernatremia developed in 4 patients (1.3%) receiving isotonic fluids; in total, this group had 61 of 308 patients [20%]) with electrolyte disturbance, compared with 9 of 306 patients [2.9%] of those receiving hypotonic fluid therapy (P < .001)
    • “Severe” hypokalemia (<3.0 mmol/L) was significantly more common in patients receiving isotonic fluid therapy 8 of 308 patients (2.6%) compared with 1 of 306 patients ( 0.3%) patients receiving hypotonic fluid therapy

My take: In the U.S., this suggests that fluids like lactated ringer’s which also has a low amount of potassium should not be routinely used. When choosing an isotonic fluid in children, D5 Normal Saline (0.9%) with added potassium may be more suitable..

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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

#NASPGHAN18 Abstract: LR for Pancreatitis & Pumpkin Shot

At NASPGHAN18, an abstract provided more information that indicates that lactated ringer’s is probably the best intravenous fluid for most children with acute pancreatitis

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2018 Pumpkin for our House

Choosing the Right Intravenous Fluids

A recent “SALT-ED” study (WH Self et al. NEJM 2018; 378: 819-28) with more than 13,000 noncritically-ill adults indicated that patients who received normal saline had increased incidence of major adverse kidney events compared to those who received more balanced fluids like lactated Ringers’ or Plasma-Lyte A.

A 2 min quick take summary:Comparison of Crystalloids and Saline for Noncritically Ill

In a separate “SMART” study (MW Semler et al. NEJM 2018; 378: 829-39), investigators looked at balanced crystalloids versus saline in critically-ill adults (n=15,802).  The use of balanced crystalloids (compared to saline) resulted in a lower rate of mortality (10.3% vs 11.1%, P=.06) and fewer major adverse kidney events (14.3% vs. 15.4%, P=.04).

 

Acute Pancreatitis: Clinical Report from NASPGHAN

There are no surprises in a recent clinical report on acute pancreatitis (M Abu-El-Haija et al. JPGN 2018: 66: 159-76) from NASPGHAN.

Here are a few of the points:

  • The authors recommend ultrasound for initial imaging and checking liver enzymes, GGT, calcium and triglycerides.
  • For fluids, they indicate that in adults there is evidence suggesting that lactated ringer’s (LR) is likely preferable to normal saline.  In children, on presentation, “if evidence of hemodynamic compromise, a bolus of 10 to 20 mL/kg” of crystalloid is recommended followed by “1.5 to 2 times maintenance IV fluids.”
  • For pain management not responding to acetaminophen or NSAIDs, “IV morphine or other opioids should be used.”
  • They recommend early oral/enteral nutrition (within 48 to 72 hours of presentation).
  • They recommend against prophylactic antibiotics in severe acute pancreatitis.
  • They recommend against probiotics, anti-proteases, and antioxidant therapy.
  • For fluid collections that need drainage or necrosectomy, nonsurgical approaches are favored.
  • Acute biliary pancreatitis, “Cholecystectomy safely can and should be performed before discharge in cases of mild uncomplicated acute biliary pancreatitis.”

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American Ingenuity!!

Changing Practice Patterns with Pediatric Pancreatitis

A recent study (FK Szabo et al. J Pediatr 2015; 167: 397-402) supports the practice of early enteral nutrition and aggressive fluid administration with acute pancreatitis. Starting in January 2014, Cincinnati Children’s began using high rates of intravenous fluid and resuming enteral nutrition within 48 hours for children presenting with acute pancreatitis.  This retrospective study assessed this practice in 201 patients and compared with prior experience dating back to 2009. To be included, patients had to have mild acute pancreatitis based on the Atlanta criteria (Gut 2013; 62: 102-11). Exclusion criteria:

  • Severe acute pancreatitis: multiorgan failure, systemic inflammatory response, local pancreatic complications (eg. necrosis, hemorrhage, pseudocyst), or respiratory complications
  • Pancreatitis due to trauma, gallstones or postsurgical

With regard to enteral nutrition (EN), nasoenteric tubes were not placed during the first 48 hours, but preexisting enteral tubes were used. So, most patients were orally fed. With regard to IV fluids, 62% received 1.5-2 times the maintenance IVF during the first 24 hours of admission.  More than 90% of cases received dextrose 5% normal saline. Key Findings:

  • Length of stay was 2.9 days in the early EN group compared with 4.4 days in the NPO group (P <.0001).  It is noted that the NPO group did include 24% with severe acute pancreatitis compared with 6% in the early EN group.
  • The authors did not identify any change in measured outcomes based on high or low volume IVF.

From the discussion:

  • “EN remains an integral part of management which has been associated with a lower incidence of infection, multiorgan failure, lower mortality rates, and a shorter hospital stay in adult patients with AP [acute pancreatitis]”
  • “Our study shows that oral feeds represent a safe and a feasible strategy in mild AP.” There was not an increase in readmission rates within 72 hours of discharge, either.

Because this is a retrospective study, this limits the interpretation of these findings; there could be an element of reverse causation with regard to the outcomes.

My take: Increasing evidence supports the practice of early enteral feedings in mild acute pancreatitis.  The exact IV fluids to use remain unclear, though my preference is lactated ringer’s based on ERCP-induced pancreatitis studies.

Related blog posts:

  • Why an ERCP Study Matters to Pediatric Care | gutsandgrowth This post explains why LR may be best.
  • Nutrition University / gutsandgrowth What are the nutritional management recommendations for acute pancreatitis? Justine Turner indicated that too many centers continue to rely on parenteral nutrition.  Yet, guidelines recommend the use of enteral nutrition due to lower risk of poor outcomes (eg. infections when NPO and on parenteral nutrition). ‘Resting pancreas is not helpful.’ With acute pancreatitis, enzyme secretion is reduced.  Her approach is to start nasogastric (NG) feedings at about 24 hours after presentation, as long as hemodynamically stable.  She indicated that nasojejunal (NJ) feedings can be done if NG is not well-tolerated.  NJ feedings are effective at reducing enzyme secretion.  However, Praveen Goday stated that his practice was often starting with NJ feeds.  “Sometimes there is only one shot” before the ICU team starts HAL.  Both physicians indicated that polymeric formulas were probably acceptable; however, starting with semi-elemental or elemental feedings are often done, again as a practical matter to minimize the likelihood of reverting to parenteral nutrition.

Artist Point, Yellowstone

Artist Point, Yellowstone

“We Still Have More to Learn”

“The most beautiful thing we can experience is the mysterious, it is the source of all true art and science. He to whom this emotion is a stranger, who can no longer pause to wonder and stand rapt in awe, is as good as dead: his eyes are closed.” –Albert Einstein.

I’m not sure the above quote has much direct relevance to today’s blog, but it came to mind after reading “we still have more to learn” in a recent editorial.  The editorial elaborated on another study showing that hypotonic fluids increase the risk of hyponatremia (J Pediatr 2014; 165: 163-9, editorial 14-15).  The editorial cautions that “intravenous fluid therapy is a prescription much like antibiotics or chemotherapy.  What we prescribe for intravenous fluids must fit the patient’s history and condition.”

The article was a systemic review of published studies.  Though 1634 citations were screened, only 10 studies (n=893) were included as independent randomized controlled trials.  Hypotonic fluids were defined as tonicity <250 mmol/L; isotonic fluids were defined as normal saline (0.9%), Ringer lactate, Hartmann solution, and any other fluid with tonicity approaching that of normal serum. The key findings:

  • Hypotonic fluids increase the relative risk (RR) of hyponatremia (Na <135) with RR of 2.37
  • Moderate hyponatremia (Na <130) risk was increased further with RR of 6.1.
  • Sub-group analysis of half-normal saline showed relative risk for hyponatremia was 2.42.

The editorialists comment that much has changed in the 55+ years since Holliday and Segar’s publication in 1957 describing maintenance fluid requirements.  These changes include sicker patients who are at increased risk for non-osmotic ADH release.  Thus, even patients receiving isotonic fluids are at some risk for hyponatremia.  However, the key point is that maintenance fluids are not appropriate for replacement of losses and in the perioperative setting.

Bottomline: Think twice before using a hypotonic fluid especially on admission or after surgery.  While there is no perfect intravenous fluid for all patients at all times, in many patients, isotonic fluids will be more favorable by reducing the risk of hyponatremia.

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Unrelated link:

In Treating Crohn’s Disease, Earlier is Better | – AGA Journals Blog

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.

  1. Clin Gastroenterol Hepatol 2014; 12: 303-07.
  2. Clin Gastroenterol Hepatol 2014; 12: 308-10 Associated editorial
  3. Gastroenterol 2014; 146: 581-82. Associated summary

Key points/Implications:

  • 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.

Study details:

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%).

Results:

  • 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.

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