Why might Lactated Ringer’s (LR) solution be preferred over normal saline (NS) for fluid resuscitation in acute pancreatitis?

Although the data is limited, fluid resuscitation with lactated Ringer’s (LR) solution in acute pancreatitis has been associated with lower risk of persistent systemic inflammatory response syndrome (SIRS) compared to normal saline (NS),  with an additional trend toward lower mortality.1-3

A 2018 meta-analysis of 3 randomized-controlled trials (RCTs) and 2 retrospective studies involving 428 patients found a significantly lower odds of developing SIRS at 24 hours (OR 0.38, CI 0.15-0.98).   Mortality was also lower in the LR group (OR 0.61, 95% CI 0.28-1.29), though it did not reach statistical significance. 1

A small 2011 RCT was the first to suggest the “protective” effect of LR in acute pancreatitis, reporting significant reduction in the prevalence of SIRS after 24 hours when compared to NS (84% vs 0%);  patients on LR also had a significantly lower C-reactive protein (CRP) (104 mg/L vs 51.4 mg/L) at 24 hours. 2   Significantly lower CRP levels were also reported at 48 and 72 hours when LR was compared to NS in another RCT in acute pancreatitis.3

As for potential mechanisms for the observed beneficial effects of LR on the pancreatic tissue in acute pancreatitis, hyperchloremic metabolic acidosis (with its attendant low extracellular pH) often seen in large volume NS resuscitation was initially thought to contribute to pancreatic injury.2  A more plausible explanation, however, may relate to the direct anti-inflammatory effect of lactate itself.  Of interest, lactate has been shown to inhibit macrophage induction invitro 4  and suppress innate immunity in experimental models of pancreatitis. 3 Who would have guessed!

Bonus Pearl: Did you know that Ringer’s solution gets its name from Sydney Ringer, a 19th century physician who demonstrated the importance of salts of sodium, potassium, calcium and chloride in precise proportions for cellular function?  LR solution was actually concocted in the 1930s by a St. Louis pediatrician, Alexis Hartmann, and was also known as the “Hartmann’s solution”. 4

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References

  1. Iqbal U, Anwar H, Scribani M. Ringer’s lactate versus normal saline in acute pancreatitis: A systematic review and meta-analysis. J Dig Dis 208;19:335-341. https://onlinelibrary.wiley.com/doi/epdf/10.1111/1751-2980.12606
  2. Wu BU, Hwang JQ, Gardner TH, et al. Clin Gastroenterol Hepatol 2011;9:710-17. https://www.cghjournal.org/article/S1542-3565(11)00454-X/abstract
  3. de-Madaria E, Herrera-Marante I, Gonzalez-Camacho V, et al. Fluid resuscitation with lactated Ringer’s solution vs normal saline in acute pancreatitis: A triple-blind, randomized, controlled trial. UEG J 2017;6:63-72. file:///C:/Users/manifa/OneDrive%20-%20Mercy%20Online/pancreatitis%20LR2spain.pdf
  4. Lee JA. Sydney Ringer (1834-1910) and Alexis Hartmann (1898-1964). Anaesthesia 1981;36:1115-21. https://associationofanaesthetists-publications.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2044.1981.tb08698.x

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis or its affiliate healthcare centers. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

 

Why might Lactated Ringer’s (LR) solution be preferred over normal saline (NS) for fluid resuscitation in acute pancreatitis?

Is there an association between infections and falls?

Although the list of factors that lead to falls is long and varied, increasing number of reports have identified falls as a manifestation of infections, including Covid-19.1-4

A retrospective study involving over 1400 patients (mean age 72 years) admitted to the hospital for a fall or its complications found coexisting systemic infections (CSIs) in 21% of patients; 26% in those ≥75 years. Urinary tract infection accounted for 55% of CSIs, followed by pneumonia (36%), skin and soft tissue infections (7%), influenza/influenza-like illness (5%), bacteremia (5%), gastrointestinal infections (2%), and others. 1

Risk factors for CSI include preexisting symptoms (eg, weakness, dizziness), inability to get up on own, confusion, age ≥ 50 years and meeting the systemic inflammatory response syndrome (SIRS) criteria on presentation.1 Of note, CSI may not initially be suspected by providers in about one-third or more of the cases, with 15% of patients presenting with “mechanical fall” having a CSI.1,2  Fever or SIRS criteria (≥2) are absent in the majority of patients with CSI.1,2

More recently, reports of falls as a presenting feature of Covid-19 have also appeared in the lay press as well as the literature, with 1 study finding 24% of patients with Covid-19 seek care primarily because of syncope, near syncope, or a nonmechanical fall.3,4

Several factors may explain the association of infections with falls, including impairment of skeletal muscle function (eg, through cytokines, hypophosphatemia), poor oral intake and dehydration. 1 Perhaps that’s why inability to get up by one’s self from a fall in the absence of an obvious reason (eg, fracture) may be a clue to a CSI in patient presenting with a fall.

Bonus Pearl: Did you know that falls are a leading cause of injury and death, afflicting one-third of adults aged greater than 65 years each year?1

Disclosure: The author of this blog also was a coinvestigator in 2 cited studies (ref. 1 and 2)

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References

  1. Manian FA, Hsu F, Huang D, et al. Coexisting systemic infections in patients hospitalized because of a fall: prevalence and risk factors. J Emerg Med 2020;58:733-40. https://www.sciencedirect.com/science/article/abs/pii/S0736467920300214
  2. Blair A, Manian FA. Coexisting systemic infections in patients who present with a fall. Am J Med Sci 2017;353:22-26. https://pubmed.ncbi.nlm.nih.gov/28104099/
  3. Chen T, Hanna J, Walsh EE, et al. Syncope, near syncope, or nonmechanical falls as a presenting feature of COVID-19. Ann Emerg Med 2020 July;76:115-117. https://pubmed.ncbi.nlm.nih.gov/32591120/
  4. Norman RE, Stall NM, Sinha SK. Typically atypical: COVID-19 presenting as a fall in an older adult. J Am Geriatr Soc 2020 July;68:E36-37. DOI:10.1111/gs.16526 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7267373/pdf/JGS-9999-na.pdf

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Is there an association between infections and falls?

What are the major changes in the definition of “sepsis” under the 3rd International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)?

Under Sepsis-3 [1], sepsis is defined as a “life-threatening organ dysfunction caused by a dysregulated host response to infection (suspected or confirmed)”. Systemic inflammatory response syndrome (SIRS) is no longer defined as part of the sepsis spectrum, and its criteria have been replaced by the Sequential Organ Failure Assessment (SOFA) with a change in score ≥2 (Table) having >10% in-hospital mortality. Septic shock is defined as hypotension requiring vasopressors to maintain a MAP ≥65 mm Hg and a lactate >2 mmol/L (18 mg/dL) despite adequate volume (>40% in-hospital mortality).

A bedside clinical tool “quickSOFA” (qSOFA), not meant to substitute for SOFA, is also proposed to identify patients primarily outside of the ICU who may be at high risk of adverse outcomes, based on the following criteria: systolic blood pressure ≤100 mmHg, respiratory rate ≥22/min, and altered mental status. A qSOFA score ≥2 is associated with poorer outcomes [1,2].

So what do these new guidelines mean for clinicians? Under the new terminology, “sepsis” now refers only to what was previously considered severe sepsis with or without shock, and those who may need more aggressive therapy, closer monitoring and possible transfer to an ICU [1,2]. As the guidelines stress, however, failure to meet qSOFA or SOFA criteria should by no means lead to a deferral or delay in evaluation or treatment of infection deemed necessary by clinicians, and SIRS criteria may still be useful in identification of infection [1].

It remains to be seen whether limiting the definition of sepsis to only patients with associated organ dysfunction will translate into an overall earlier diagnosis and improved prognosis for this condition.

Using SIRS criteria (ie, 2 or more of the following, heart rate >90/min, respiratory rate >20/min  or PaC02 <32 mm Hg, temperature<36 C or >38 C, WBC <4,000 or >12,000 or bandemia >10%) in patients suspected of having a potentially serious infection still makes sense if the goal is to identify it “upstream” before organ dysfunction or shock sets in.  Stay tuned!

 

Table. Sequential (sepsis-related) organ failure assessment (SOFA) score (adapted from ref.1)____________________________________________________________________________________________________

                                                                                             Points

Parameter                                0                      1                      2                      3                      4

____________________________________________________________________________________________________

Pa02/Fi02                           ≥400                 <400                <300                 <200*          <100*

Platelets (no./mL)           >150,000         <150,000         <100,000         <50,000       <20,000

Bilirubin (mg/dL)            <1.2                  1.2-1.9              2.0-5.9             6.0-11.9       >12.0

MAP (mm Hg) or VP      MAP≥70         MAP<70          DPA≤5           DPA 5.1-15        DPA>15

Glascow Coma Scale       15                    13-14            10-12                    6-9                 3-6

Creatinine (mg/dL)        <1.2                 1.2-1.9           2.0-3.4                  3.5-4.9        >5.0

OR U.O.  (mL/dL)                                                                                              <500                <200

____________________________________________________________________________________________________

MAP= mean arterial pressure, VP=vasopressor (includes agents other than dopamine), DPA=dopamine (in mcg/kg/min for ≥1 hour);U.O.= urine output

*With respiratory support

 

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References:

  1. Singer MS, Deutschman CS, Seymour CW, et al; The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315[8]:801-810. https://jamanetwork.com/journals/jama/fullarticle/2492881  
  2. Jacob JA. New Sepsis Diagnostic Guidelines Shift Focus to Organ Dysfunction. JAMA. 2016;213[8]:739-740. https://www.ncbi.nlm.nih.gov/pubmed/26903319

 

Contributed by Erik Kelly MD, Mass General Hospital, Boston, MA

What are the major changes in the definition of “sepsis” under the 3rd International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)?