Saline Shortages

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Two interesting commentaries on the saline shortages:

  • M Mazer-Amirshahi, ER Fox. NEJM 2018; 378: 1472-4.
  • AM Patino et al.  NEJM 2018; 378: 1475-7.

The first explains that large quantities of saline bags are needed each month –more than 40 million bags per month!  While saline is inexpensive, the production requires meticulous care to avoid contamination and there have been supply issues since 2014, prior to Hurricane Maria.  However, the problem has been much worse since Hurricane Maria which damaged Puerto Rico.  Puerto Rico supplies 44% of the IV bags in the U.S.  These fluids are given to virtually all hospitalized patients, either for IV fluids or as a component with medications/flushes.

Other points:

  • “Drug manufacturers are not required to have redundancy in their facilities or even a business contingency plan in case of a disaster.”
  • The  FDA has “recently approved saline products from two additional manufacturers”
  • “To conserve large-volume saline bags, oral hydration is recommended.”

The article by Patino et al provides Brigham and Women’s Hospital Oral Rehydration protocol. Key points:

  • Using their protocol, the volume of IV fluid use decreased over 30% in the first week of implementation
  • The fraction of ED patients using IV fluids dropped by 15% in the first 3 weeks of implementation.
  • Oral hydration protocols are a “rational practice change…even after the current IV-fluid shortage crisis ends.”

 

Reliability of High Serology in Asymptomatic Celiac Disease

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Another study (SP Paul et al. JPGN 2018; 66: 641-44) has shown that high anti-TTG IgA levels are reliable in establishing the diagnosis of celiac disease in asymptomatic children from high-risk groups. In this study with prospectively-collected data from 2007-2017, 84 of 157 children had anti-TTG titers >10x ULN.  75 of these 84 were from high-risk groups, mainly type 1 diabetes (36), and first degree relatives (24)

Key finding:

  • All 75 with high titers from high-risk groups had histologic evidence of celiac disease.

Related blog posts:

Related study: R Mandile et al. JPGN 2018; 66: 654-56. This prospective study showed that 19 of 35 (54%) patients with potential celiac disease had a complete clinical response on a gluten-free diet to symptoms like abdominal pain and diarrhea.  Thus, in many patients with potential celiac disease, a gluten-free diet will not be effective.

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PEG 3350 is Not Associated with Elevated Glycol Levels

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Everyday parents ask me if Miralax (polyethylene glycol) is safe; this has been driven by social media claims of neurotoxicity and by articles in the NY Times (see prior blog references) indicating that more testing is needed.

A recent study (KC Williams et al. J Pediatr 2018; 195: 148-53) examines one of the areas of concern, whether miralax could result in toxic levels of glycols.  In this study with 9 treated children (ages 6-12 years) and 18 controls, careful study of potentially toxic agents, ethylene glycol (EG), diethylene glycol (DEG), and triethylene glycol (TEG), were measured every 30 minutes for 3 hours after receiving 17 g of PEG 3350.

Key findings:

  • Baseline blood levels of EG (390.51 ng/mmL) and TEG (2.21 ng/mL) did not differ between control and treated groups
  • Baseline DEG levels were lower in the PEG 3350 group (40.12 ng/mL vs 92.83 ng/mL, P=.008)
  • After PEG 3350 dose, EG and TEG levels remained well below toxic levels; DEG levels did not change.  The increases in EG and TEG, which peaked at 90 minutes, were not sustained at levels different from controls.
  • EG peaked at 1032.8 ng/mL. TEG peaked at 35.17 ng/mL
  • The highest levels of EG and DEG were actually identified in control patients. Thus, “all children are exposed routinely and have measureable amounts in the blood.”

With regard to TEG toxicity, in the discussion, the authors note that, based on animal studies, “very large doses of TEG are needed to cause side effects.” Even doses of 4000 mg/kg of TEG daily for 90 days did not result in local or systemic toxicity.  The authors note that TEG concentration in PEG 3350 is “approximately 22.1-30.6 mcg per 17 gram dose of PEG 3350.”

With regard to EG and DEG, “the average EG and DEG content of the PEG samples in this study were a 100 and 800 times less, respectively, than this required 0.2% cutoff” [FDA limit].  The agency of Toxic Substances and Disease Registry profile for EG, has indicated that “EG blood levels greater tan 0.2 mg/mL are needed for acute toxic poisoning.  The average level of EG at the 90-minute peak of 1100 +/- 350 ng/mL was 182 times lower than this level.”  For chronic exposure EG toxicity, the authors estimate that one would need to take “40 capfuls [17 gram each] of PEG 3350 per day for up to a year.”  The EPA also has advisories with regard to EG.  To achieve toxic levels for a 10-kg child, this would necessitate that the child “would have to drink 1 L of water with 50 capfuls (858 g) in 1 day or 15 capfuls (258 g) per day for 10 days.”

An important limitation of this study is that there may be other metabolites that are not measured that could cause neurotoxicity.

My take: This study shows that the theoretical risk of glycol toxicity is highly unlikely.  My advice for miralax usage: (borrowed from expert review): “Generally speaking, if your child has been prescribed PEG 3350 as part of his/her treatment plan, and you feel this medicine provides benefit, you should feel safe continuing PEG 3350. At this time, PEG 3350 appears to be safe based on current medical literature. We recommend discussing any concerns you have about the safety of PEG 3350 with your child’s health care provider. If you would prefer for your child to stop taking PEG 3350, discuss other treatments options with your child’s health care team before stopping PEG 3350 therapy. Although abruptly stopping PEG 3350 is not considered dangerous, it could lead to a relapse/worsening of constipation.”

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  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.

Related blog posts:

Fast Track Recovery/Enhanced Recovery After Surgery (ERAS is Awesome!)

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At a recent ImproveCareNow population management meeting for our group, Dr. Kurt Heiss provided an update on the expanding use of ERAS.  In addition to colorectal surgery, uses at our hospital system have included bariatric surgery, craniofacial surgery, and umbilical hernia repairs. The results of this bundled care show fewer complications, less pain/less narcotics (more blocks), and shorter hospital stays (without increased readmission rates).

For those who are not as familiar as they would like (and for patients), I recommend a 7 minute Lego ERAS YouTube link: LEGO Surgery -Enhanced Recovery After Surgery

Related blog post: ERAS -Enhanced Recovery After Surgery (2016) With full slide set explaining ERAS further

 

 

Assessment of Organ Donation –MRI Often Precludes Need for a Liver Biopsy

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A recent retrospective single-center study (J Satkunasingham et al. Liver Transplantation 2018; 24: 470-77) shows that MRI is a good tool to assess hepatic steatosis.  In total there were 144 liver donor candidates; a subset of 32 underwent liver biopsy.

When examining magnetic resonance spectroscopy (MRS) and MRI -proton pump density fat fraction (PDFF), the authors found that MRS-PDFF and MRI-PDFF had 95% and 100% negative predictive value in identifying patients with clinically  significant histologic steatosis (≥10%).

The associated editorial by James Trotter (pg 457-58) makes several important points:

  • Currently living donor transplantation in the U.S. accounts for 4% of all transplants
  • In his center (and most centers), protocol biopsy are not required prior to liver donation.  The main indications for donor liver biopsy are biochemical dysfunction or steatosis on imaging studies.

My take (borrowed from editorial): “Noninvasive estimation of hepatic steatosis is sufficiently accurate to forgo liver biopsy in most donors, although ultimately this decision will continue to rest with the individual center.”

 

Opiates, Inflammatory Bowel Disease and Mortality

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A recent retrospective study (NE Burr et al. Clin Gastroenterol Hepatol 2018; 16: 534-41) with 3517 patient’s with Crohn’s disease (CD) and 5349 with ulcerative colitis (UC) examined the frequency of opioid prescriptions and the relationship to fatal outcomes.

Key findings:

  • Compared to 1990-93, the period of 2010-13 saw a sharp rise in the use of opiods in England: 10% compared to 30%.
  • Prescription of strong opioids (>3 prescriptions per calendar year) was associated with premature mortality: Hazard ratio 2.18 for CD and 3.3 for UC.

This study is in agreement with other data showing increasing use of opiate prescriptions worldwide for chronic noncancer pain (although there has been a drop in the past year).  As with other studies of patients with inflammatory bowel disease, this study shows an association between opioid use and mortality.

My take: Needing an opioid may be a marker for more severe disease. Whether the opioid use directly contributes to mortality remains unclear.

 

When Should a Spleen Guard Be Recommended?

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A survey (O Waisbourd-Zinman, et al. JPGN 2018; 66: 447-49) of 44 pediatric hepatologists (with 935 years of clinical practice) examined the issue of splenic rupture and spleen guards.  ~90% of those surveyed reported following at least 30 patients with portal hypertension and splenomegaly.

  • In total, the hepatologists could recall 13 cases of splenic rupture among patients with portal hypertension/splenomegaly due to cirrhosis –almost all of these occurred after a fall or in a motor vehicle accident.  Only one of these falls happened during a sports-related event (soccer).
  • 11 cases were serious. 9 of these cases resulted in shock with subsequent splenectomy, embolization, and/or death. Death reported in 2 cases.
  • In this survey,  61% of hepatologists recommended “absolute restriction from activity with high risk of blunt abdominal trauma;” whereas 23% indicated that activities with risk of blunt trauma were acceptable if wearing a spleen guard.
  • To prevent splenic rupture in patients with portal hypertension/splenomegaly, among the participating hepatologists, the majority identified the following ‘high risk’ sports: football (95%), hockey (82%), and wrestling (66%).  A smaller percentage advocated a spleen guard for skiing (42%), soccer (41%), basketball (30%) and other sports.

While I did not participate in this survey, the one patient with chronic liver disease that I followed who had a splenic rupture had fallen down a flight of steps; fortunately, he recovered with supportive care.

My take: This survey shows that there is wide variability in the use of spleen guards.  In almost all cases of splenic rupture, this was precipitated by severe trauma.  Though, patients with portal hypertension may avoid high contact sports and thus the risks are for these sports is unclear.

Related blog post:

Foggy Morning in Sandy Springs

113 Recommendations for Crohn’s Disease Management from ACG

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Full Text Link: ACG Clinical Guideline: Management of Crohn’s Disease. GR Lichtenstein et al. Am J Gastroenterol 2018; 113:481–517

A few of the recommendations from Table 1:

  • (Insurance companies –please read this one): #1 Fecal calprotectin is a helpful test that should be considered to help differentiate the presence of IBD from irritable bowel syndrome (IBS) (strong recommendation, moderate level of evidence).
  • #9 Perceived stress, depression, and anxiety, which are common in IBD, are factors that lead to decreased health-related quality of life in patients with
    Crohn’s disease, and lead to lower adherence to provider recommendations. Assessment and management of stress, depression, and anxiety should be
    included as part of the comprehensive care of the Crohn’s disease patient (strong recommendation, very low level of evidence)
  • #24, 25 Anti-TNF agents (infliximab, adalimumab, certolizumab pegol) should be used to treat Crohn’s disease that is resistant to treatment with corticosteroids (strong recommendation, moderate level of evidence). Anti-TNF agents should be given for Crohn’s disease refractory to thiopurines or methotrexate (strong recommendation, moderate level of evidence).
  • #26 Combination therapy of infliximab with immunomodulators (thiopurines) is more effective than treatment with either immunomodulators alone or
    inflximab alone in patients who are naive to those agents (strong recommendation, high level of evidence).
  • #27 For patients with moderately to severely active Crohn’s disease and objective evidence of active disease, anti-integrin therapy (with vedolizumab) with
    or without an immunomodulator is more effective than placebo and should be considered to be used for induction of symptomatic remission in patients with
    Crohn’s disease (strong recommendation, high level of evidence).
  • #30 Ustekinumab should be given for moderate-to-severe Crohn’s disease patients who failed previous treatment with corticosteroids, thiopurines, methotrexate, or anti-TNF inhibitors or who have had no prior exposure to anti-TNF inhibitors (strong recommendation, high level of evidence).
  • #46 Oral 5-aminosalicylic acid has not been demonstrated to be effective for maintenance of medically induced remission in patients with Crohn’s disease,
    and is not recommended for long-term treatment (strong recommendation, moderate level of evidence).
  • # 58 In high-risk patients, anti-TNF agents should be started within 4 weeks of surgery in order to prevent postoperative Crohn’s disease recurrence
    (conditional recommendation, low level of evidence).

From Table 2:

  • #9 Symptoms of Crohn’s disease do not correlate well with the presence of active inflammation, and therefore should not be the sole guide for therapy. Objective evaluation by endoscopic or cross-sectional imaging should be undertaken periodically to avoid errors of under– or over treatment.
  • #23 Routine use of serologic markers of IBD to establish the diagnosis of Crohn’s disease is not indicated.
  • #30 Small bowel imaging should be performed as part of the initial diagnostic workup for patients with suspected Crohn’s disease.
  • #44 Insufficient data exist to support the safety and efficacy of switching patients in stable disease maintenance from one biosimilar to another of the same biosimilar molecule.

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  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.

EPA OK with “Polluting Developing Brains”

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For those unable to grasp the fact that the current EPA director is harmful to our health, it may not be their fault.  According to this commentary (VA Rauh. N Engl J Med 2018; 378:1171-1174), organophosphates like chlorpyrifos have likely resulted in the loss of ~17 million IQ points among 0 to 5 year olds; by extrapolation, this affects those older than 5 years too. Link: Polluting Developing Brains — EPA Failure on Chlorpyrifos

An excerpt: The regulatory plan developed by the U.S. Environmental Protection Agency (EPA) just before the 2016 elections was excellent: revoke all allowances for foods to contain residue of the organophosphate insecticide chlorpyrifos (“food tolerances”), essentially prohibiting agricultural and all remaining uses of the chemical… A total ban was the logical conclusion after decades of risk assessment showing increasing evidence of threats to human health, and children’s safety in particular…

However, the plan was scrapped in March 2017 by incoming EPA Administrator Scott Pruitt, who overrode the recommendation of agency scientists to ban all commercial use of chlorpyrifos… this action essentially violates the EPA’s statutory duty to protect human health, ignoring explicit child health policy dating back to 1995 that requires all national public health standards to address the special vulnerability of infants and children…

Harmful effects of chlorpyrifos on the developing brain are hardly surprising, given that this chemical was initially developed to attack the nervous system by inhibiting neurotransmitters in the body. First introduced as nerve-gas agents during World War II, organophosphate chemicals were later repurposed by chemical companies as insecticides and other pesticides…

Among the most worrisome findings are the corroborative results from several prospective cohort studies of children, which show an inverse dose–response effect of prenatal exposure to chlorpyrifos on cognition at 7 years of age..

In fact, one review (assuming a population of 25.5 million children 0 to 5 years of age in the United States) calculates a total loss of 16.9 million IQ points due to exposure to organophosphates, of which chlorpyrifos is the most widely used..

Because adult occupational exposures to chlorpyrifos have been clearly linked to Parkinson’s disease, there is good reason to worry that early exposures may set in motion a pathogenic trajectory potentially leading to neurodegenerative disease…

The EPA …may be putting an entire generation of young brains in harm’s way.

Estimated Agricultural Use for Chlorpyrifos, 2015 (Preliminary).
Estimates are from the U.S. Geological Survey National Water-Quality Assessment Project.

Wilson’s Disease –Pediatric Guideline

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P Socha et al. JPGN 2018; 334-4. This ESPGHAN position paper makes recommendations for Wilson’s disease. This is a helpful paper, though the AASLD Wilson’s guideline is more comprehensive. A couple of pointers from the JPGN publication:

  • The authors recommend molecular testing if available and using liver copper measurement “if molecular testing is inconclusive”
  • Screen siblings of any new patients
  • Urinary copper excretion in the 200-500 mcg per 24 hours is consistent with adequacy of treatment
  • With treatment, liver function tests improve over 2-6 months. “If increased transaminases remain or relapse despite treatment, poor compliance should be suspected.”

Related blog posts:

 

January 2018 -Sunrise in Sandy Springs