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..

Related blog posts:

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

“Socialism” is Already Here & Increasing in U.S. Health Care

The U.S. government now pays for nearly 50% of health care expenditures (Government Now Pays For Nearly 50 Percent Of Health Care Spending, An Increase Driven By Baby Boomers Shifting Into Medicare, Kaiser Health News, 2/21/19). Both in adults and children, the share of public sector spending is increasing. The biggest areas of costs include Medicare, Medicaid, CHIP and Veterans health care. The U.S. government also funds the HHS which includes the FDA, NIH, CDC, and AHRQ.

A recent commentary (JM Perrin et al. NEJM 2020; 383: 2595-2598. Medicaid and Child Health Equity) describes what is happening with Medicaid and the Children’s Health Insurance Program (CHIP).

Key points:

  • Over the past 20 years, the proportion of pediatric health care coverage provided by Medicaid and CHIP has been increasing. In 1997, these programs represented about 15% of health care coverage compared to ~35% in 2018. This corresponds to reductions in employer-provided coverage
  • Unlike private insurance, Medicaid is always available as it doesn’t have fixed enrollment periods
  • Medicaid disproportionately covers minority populations
  • State funding of Medicaid creates challenges. “States have routinely used strategies for limiting enrollment”
  • “Medicaid’s low physician payment rates, which average about two-thirds of rates paid by Medicare for the same services, depress physician participation…Lack of access to specialists poses additional problems in many communities”
  • The authors recommend the following:
    • Medicaid should be expanded to cover all children from birth through 21 years of age
    • The federal government should assume full financial responsibility
    • Medicaid payments should parallel national Medicare standards

Related blog posts:

Very Low Risk of Malignancy with Celiac Disease and Even Lower After Starting a Gluten Free Diet

A recent study (L Emilsson et al. Gastroenterol 2020; 159: 1686-1694. Full/open access: Risk of Small Bowel Adenocarcinoma, Adenomas, and Carcinoids in a Nationwide Cohort of Individuals With Celiac Disease) quantifies the risk of small bowel adenocarcinoma in individuals with celiac. Using a Swedish nationwide cohort with a median follow-up of 11 years, the authors identified 48,119 individuals with CD (patients) and 239,249 reference individuals.

Key findings:

  • Beginning at 1 year after a diagnosis of CD, 29 patients (0.06%) received a diagnosis of small bowel adenocarcinoma vs 45 reference individuals (0.02%).
  • HRs were small bowel adenocarcinoma 3.05, carcinoids 0.59, and adenomas 5.73.).
  • Overall, there was 1 extra case of small bowel adenocarcinoma in every 2944 patients with CD followed for 10 years.
  • There was an inverse association between mucosal healing risk of future small bowel adenocarcinoma (HR, 0.18; 95% CI, 0.02–1.61), although the HR failed to attain statistical significance.

My take (mostly borrowed from authors): There is a tiny increase in risk of “small bowel adenomas and adenocarcinomas in patients with diagnosed CD, but only a very marginal increase in terms of absolute risk. Our results do not imply a need for surveillance but celiac individuals with signs or symptoms of malignancy should merit further investigation for small bowel adenocarcinoma. Mucosal healing was strongly associated with lower risk of small bowel adenocarcinoma, although the association failed to reach statistical significance.’

Related blog posts:

Getting Lost in the Pathophysiology of Inflammatory Bowel Disease

A recent review (JT Chang. NEJM 2020; 383: 2652-2664. Pathophysiology of Inflammatory Bowel Diseases) provides an in-depth description of the pathophysiology of inflammatory bowel disease (IBD). Digesting the article is akin to putting together a 1000 piece puzzle due to the complex interactions.

Some of the Key Points:

  • Based on genomewide association studies, there are “more than 240 risk variants that affect intracellular pathways recognizing microbial products (eg. NOD2); the autophagy pathway, which facilitates recycling intracellular organelles and removal of intracellular microorganisms (eg. ATG16L1); genes regulating epithelial barrier function (eg. ECM1); and pathways regulating innate and adaptive immunity (eg. IL23R and IL10).”
  • In this article, Figure 1 and 2 describe the intestinal mucosal immune system in health and disease. At baseline, this system promotes an antiinflammatory state “by virtue of active down-regulation of immune responses. For example, unlike macrophages in other parts of the body, intestinal macrophages do not produce inflammatory cytokines” after exposure to bacteria.

Other points:

  • Dysbiosis is present with IBD; however, studies have been “unable to infer causal relationships.”
  • Germ-free mice, when given fecal material from patients with IBD have increased susceptibility to colitis as compared to those who received fecal material from a healthy person.
    • Thus, this leads to potential for mitigating intestinal inflammation by modulation of the microbiome.
    • However, the authors note that humans are colonized by trillions of viral, fungal, bacterial, and eukaryotic microbes.
  • Other components of IBD pathophysiology: reduced mucus layer, increased microbial adherence, dysregulation of tight junctions/increased permeability, dysfunctional Paneth cells, TNF, IL23, IL12, IL6, IL 17A, IL17F, IL22, Interferon-gamma, integrins, JAK inhibitors, T-cells

My take: This article is a useful reference detailing the complexity of IBD pathophysiology and tries to summarize a whole textbook of information into 12 pages.

Related blog posts:

Persistent Symptoms After COVID-19, FAQs, and New Strain

A large study from Wuhan showed that after 6 months following hospitalization, most still had lingering symptoms.

Full text: C Huang et al. Lancet DOI:https://doi.org/10.1016/S0140-6736(20)32656-8; 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study

Key point: At 6 months after acute infection, COVID-19 survivors (n=1733 enrolled in study) were mainly troubled with fatigue or muscle weakness, sleep difficulties, and anxiety or depression. Patients who were more severely ill during their hospital stay had more severe impaired pulmonary diffusion capacities and abnormal chest imaging manifestations

NY Times analysis (Jan 8, 2021): 6 Months After Leaving the Hospital, Covid Survivors Still Face Lingering Health Issues

  • The most common issue was ongoing exhaustion or muscle weakness, experienced by 63 percent of the patients
  • About one-quarter of the patients reported difficulty sleeping
  • 23 percent said they experienced anxiety or depression
  • “Some of the sickest patients were excluded, so perhaps some of the outcomes that were reported would be worse if those patients were included”

NEJM Link: COVID-19 Vaccine: Frequently Asked Questions

NY Times (1/15/21): C.D.C. Warns the New Virus Variant Could Fuel Huge Spikes in Covid Cases “The new variant, called B.1.1.7, was first identified in Britain, where it rapidly became the primary source of infections, accounting for more than 80 percent of new cases diagnosed in London and at least a quarter of cases elsewhere in the country.”

Surprise, Surprise: Inadequate Physical Activity is a Predictor of Fatty Liver Disease (Plus 2)

Briefly noted:

Hepatology 2020; 72: 1556-1568. Inadequate Physical Activity and Sedentary Behavior Are Independent Predictors of Nonalcoholic Fatty Liver Disease. D Kim et al found that leisure‐time physical activity (≥150 minutes per week) demonstrated 40% lower odds of NAFLD. This study used the 2007‐2016 US National Health and Nutrition Examination Survey with 24,588 participants; the authors defined NAFLD based on three noninvasive panels.

Liver Transplantation 2020; 26: 1409-1421. Low Health Literacy Is Associated With Frailty and Reduced Likelihood of Liver Transplant Listing: A Prospective Cohort Study. T Bittermann et al showed that low health literacy was independently associated with physical frailty (adjusted odds ratio [aOR], 3.59; 95% confidence interval [CI], 1.50‐8.59; P = 0.004) and not being wait‐listed (aOR 1.96; 95% CI, 1.03‐3.75; P = 0.04).

Liver Transplantation 2020; 26: 1477-1491. Impact of Preexisting Inflammatory Bowel Disease on the Outcome of Liver Transplantation for Primary Sclerosing Cholangitis. In this retrospective study with 87 patients who underwent liver transplantation for PSC, 52 (60%) had pre-existing IBD. Key findings:

  • Excluding those who died within the first 3 months, the 10‐year patient survival and graft survival rates were 92.6% and 77.1%, respectively, in the PSC with IBD (PSC‐IBD) group and 97.1% and 83.2% in the isolated PSC group, respectively.
  • The rate of recurrent PSC was 21% in the PSC‐IBD group and 11% in the isolated PSC group

Thus, it appears that having pre-existing IBD did not significantly influence survival after transplantation.

NPR Story: How Clinic Staff Decided to Accept COVID-19 Vaccine

NPR (Jan 12, 2021): How Health Care Workers Made Up Their Minds On The COVID-19 Vaccine At One Mass. Clinic

“A doctor researched the safety of the COVID-19 vaccinations not only to counsel his patients and staff but also to make his own decision about whether to get the vaccine.

Carey Goldberg of WBUR has the story about how most of the staff at the Cambridge Health Alliance COVID-19 clinic in Somerville, Massachusetts, “got to yes.”

22 minute presentation: COVID Vaccine Primer available at NPR website is a really good presentation (for more widespread adoption)

Expecting Change in Eosinophilic Esophagitis Treatment

A recent study (EJ Laserna-Mendieta et al. Clin Gastroenterol Hepatol 2020; 18: 2903-2911. Full text: Efficacy of Therapy for Eosinophilic Esophagitis in Real-World Practice) highlights the disconnect between clinical practice and outcomes.

  • Methods: This study relied on the multicenter EoE CONNECT database—with 589 patients.
    • Clinical remission was < 50% in Dysphagia Symptom Score; any improvement in symptoms = clinical response.
    • Histologic remission was eosinophil count below 5 eosinophils/hpf; 5-14/hpf = histologic response.

Key findings:

  • Topical steroids were most effective in inducing histologic remission: 54.8% compared to 36.1% for PPIs and 18.5% for empiric elimination diet; histologic remission and response was 67.7%, 49.7%, and 48.1% respectively.
  • Topical steroids were most effective in inducing clinical and histologic remission or response (in 67.7% of patients), followed by empiric elimination diets (in 52.0%), and PPIs (in 50.2%).
  • However, PPIs were the first-line treatment for 76.4% of patients, followed by topical steroids (for 10.5%) and elimination diets (for 7.8%).

My take: This data (and others) indicate that topical steroids are most effective pharmacologic therapy; at some point, I expect that they will become the most frequently used.

Related blog posts:

“Layering two less specialized masks on top of each other can provide comparable protection [to N95]. Dr. Marr recommended wearing face-hugging cloth masks over surgical masks, which tend to be made with more filter-friendly materials but fit more loosely. An alternative is to wear a cloth mask with a pocket that can be stuffed with filter material, like the kind found in vacuum bags.”

Unrelated from NY Times: One Mask Is Good. Would Two Be Better? (Yes)

Cyclic Vomiting ED Protocol

Recently, I was reading information from the Cyclic Vomiting Syndrome Association (Winter 2020 issue). On page 12, there is a pretty good protocol for emergency department treatment with the caveat that this “represents a sample template and should be tailored based on individual needs.” In addition, this protocol was derived from an article by Venkatesan et al (Neurogastroenterology and Motility 2019; S2.https://doi.org/10.1111/nmo.13604 Full text: Guidelines on management of cyclic vomiting syndrome in adults by the American Neurogastroenterology and Motility Society and the Cyclic Vomiting Syndrome Association)

Key points from guidelines article:

  • “The committee strongly recommends that adults with moderate‐to‐severe CVS receive a tricyclic antidepressant (TCA) such as amitriptyline, as a first‐line prophylactic medication. “
  • Topiramate, Aprepitant, “Zonisamide or levetiracetam and mitochondrial supplements (Coenzyme Q10, L‐carnitine, and riboflavin) are conditionally recommended as alternate prophylactic medications, either alone or concurrently with other prophylactic medications.”
  • “For acute attacks, the committee conditionally recommends using serotonin antagonists such as ondansetron, and/or triptans such as sumatriptan or newer agents such as aprepitant (NK1 receptor antagonist) to abort symptoms.”
  • Evidence, dosing regimens, and algorithms are detailed in article

Sample ED CVS Protocol (for Adults):

____[name]____________ has an established diagnosis of Cyclic Vomiting Syndrome
Operational definition
* A recurring pattern of discrete episodes of severe vomiting, accompanied by profound nausea and/or severe abdominal pain
* Patient returns to usual health status between episodes (may have inter‐episodic nausea and or dyspepsia)
* In some patients, CVS episodes resemble a migraine attack
* Patients may be restless, anxious, and distressed
* Patients are not customarily dehydrated until late in the episode
Therapeutic goal
Rapid recognition and intervention may decrease severity of the attack and promote prompt resolution of symptoms
ED management
1. Clinical assessment: Pulse/Temp/BP/Weight, consciousness, and hydration
2. Laboratories/evaluation:
CBC, urea, creatinine, LFT’s, lipase, glucose, and electrolytes
EKG
Urine analysis
Diagnostic imaging at discretion of attending physician
Treatment
1. Intravenous fluids
a. IV saline bolus if clinically dehydrated
b. IV D5NS at 100%‐150% maintenance (suggested rate is 200 cc/h for a 70 kg adult.)
2. For vomiting and nausea
a. IV ondansetron 8 mg IV × 1—may repeat q 4‐6 h if ondansetron is ineffective
b. Consider diphenhydramine 50 mg IV and metoclopramide 10 mg IV
c. Consider IV fosaprepitant 150 mg if available
3. For sedation
a. IV lorazepam 1‐2 mg and b. IV diphenhydramine 50 mg for additional sedation
4. For migraine‐like presentation
a. Sumatriptan nasal 20 mg (head forward technique) or
b. Sumatriptan subcutaneous injection 6 mg/0.5 mL
5. For pain
a. IV ketorolac 30 mg if > 60 minutes from onset; may repeat 15 mg q 6 h x 2 (maximum 60 mg/d)
b. Opioids may be considered as part of an ongoing treatment plan in refractory patientsa
Reassess
1. Treatment failure—intensify treatment as indicated above or admit patient
2. Positive treatment response—discharge
a. Continue ondansetron (soluble tablets) q 6‐8 h × 24‐48 h if initially effective
b. Continue lorazepam × 24‐48 h if initially effective
c. Continue NSAIDs for pain as needed

My take: This reference is very useful. The pediatric NASPGHAN guidelines (BUK Li et al. JPGN 2008; 47:379–393. Full text: North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Consensus Statement on the Diagnosis and Management of Cyclic Vomiting Syndrome) probably need to be updated, especially as there are newer agents available (eg. aprepitant, fosaprepitant).

Related blog posts:

Resources:

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

Genetic Testing for Fatty Liver Disease Is Not Ready For Routine Use

A recent study (H Gellert-Kristensen et al. Hepatology 2020; 72: 845-856. Combined Effect of PNPLA3TM6SF2, and HSD17B13 Variants on Risk of Cirrhosis and Hepatocellular Carcinoma in the General Population) describes genetic risk score (GRS) which can stratify the risk of developing cirrhosis and hepatocellular carcinoma.

The study utilized data and plasma markers from 110,761 individuals from Copenhagen, Denmark, and 334,691 individuals from the UK Biobank. GRS scores were from 0 to 6 based on three common genetic variants: PNPLA3, TM6SF2, and HSD17B13.

Key finding:

  • A GRS of 5 or 6 (compared to GRS of 0) for fatty liver disease confers up to a 12‐fold higher risk of cirrhosis and up to a 29‐fold higher risk of HCC in individuals from the general population

The editorial by RM Pfeiffer et al (Hepatology 2020; 72: 794-795. Genetic Determinants of Cirrhosis and Hepatocellular Carcinoma Due to Fatty Liver Disease: What’s the Score?) is very helpful in placing the findings in context.

  • Only 0.5% of individuals had a GRS of 5 or 6. “A GRS of 4 [or more] which still conveyed large risks (cirrhosis, OR =5.2; HCC, OR =3.3) was found in approximately 5% of this population.”
  • Using a GRS of 4 or more, the positive predictive value of GRS-based test in the Danish population is “0.008 for cirrhosis and 0.003 for HCC. In other words, among 1000 persons with GRS greater than or equal to 4, only 8 will develop cirrhosis and 3 will develop HCC.”

My take: This study confirms that specific genetic variants increase the risk of complications from fatty liver disease. However, poor predictive value will likely preclude routine application.