#325 Hotcakes: Fluid Wars revisited, Sleep & Weight Loss, Vitamin D, Pneumonia and HBV Vaccine Updates

March 7, 2022 | By Nora Taranto

Video

Find out whether balanced solutions beat saline in the ICU (fluid wars revisited), how sleep affects weight loss and calorie intake, whether or not Vitamin D can prevent autoimmune disease, new guidelines for pneumonia and hepatitis B (HBV) vaccination, and the utility of ultrasound to measure JVP! Time to fill your plate with a fresh stack of hotcakes! Drs. Paul Williams (@PaulNWilliamz), Rahul Ganatra (@rbganatra), Nora Taranto (@NoraTaranto), and Matt Watto (@doctorwatto) catch us up on recent practice-changing articles and guidelines! 

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Credits

• Hosted and Written by: Nora Taranto MD; Rahul Ganatra MD, MPH; Paul Williams, MD, FACP, Matthew Watto MD, FACP
• Reviewer: Matthew Watto, MD, FACP
• Executive Producer: Beth Garbitelli
• Showrunner: Matthew Watto MD, FACP
• Editor: Clair Morgan of nodderly.com

CME Partner: VCU Health CE

The Curbsiders are partnering with VCU Health Continuing Education to offer FREE continuing education credits for physicians and other healthcare professionals. Visit curbsiders.vcuhealth.org and search for this episode to claim credit. See info sheet for further directions. Note: A free VCU Health CloudCME account is required in order to seek credit.

Show Segments

• Intro, picks of the week
• Fluid wars: balance solution vs saline
• Sleep and energy intake, weight loss
• Vitamin D to prevent autoimmune disease
• New ACIP guidelines for Pneumonia and Hepatitis B (HBV) vaccines
• Ultrasound for JVP
• Outro

Hotcakes

Deep dives on practice-changing articles. 

Saline vs Balanced Fluid in ICU (Nora)

Finfer S et al; PLUS Study Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Balanced Multielectrolyte Solution versus Saline in Critically Ill Adults. N Engl J Med. 2022 Jan 18. doi: 10.1056/NEJMoa2114464. Epub ahead of print. PMID: 35041780.

Question: Are more “balanced” fluids (fluids with more physiologic concentrations of various electrolytes) better than normal saline (0.9%)?  The fluid wars have persisted in multiple spaces over the last decade, with the most recent pendulum in critical care seeming to swing more to the side of balanced crystalloids like lactated ringers or plasma-lyte over normal saline out of concern about increasing kidney injury and even all-cause mortality in patients maintained on normal saline (SMART trial 2018 being the most recent of these, though it was open-label), and no difference in other trials (SPLIT trial 2015). The BaSICS trial (2021) did not find a difference in mortality, need for renal replacement, or AKI (see NephJC discussion here). 

Comparison:  The PLUS trial was a double-blind, randomized controlled trial in critically ill adults that compared Plasma-Lyte 148 (a balanced multi-electrolyte solution) with normal saline. The primary outcome was death from any cause at 90 days, with secondary outcomes as the initiation of new renal-replacement therapy and increase in Creatinine. Patients were excluded if they had received previous fluid resuscitation (>500 mL), had life expectancy under 90 days, or were at risk of cerebral edema. Once outside the ICU, any type of fluid could be administered. 

Results and Thoughts: This was overall a negative trial. The study was performed down under, in Australia and New Zealand and followed 5037 patients, with half in each group, who received a median of 3.5-4L fluids in both groups over six days. Death within 90 days of randomization occurred in 21.8% of the balanced solution group and 22% of the saline group, a difference that did not reach statistical significance (difference -.15%, 95%, CI -3.6 to 3.3, p 0.9). For secondary outcomes: new RRT occurred in 12.7% vs 12.9% of individuals in the balanced versus saline groups, respectively (also not statistically significant), and there were not clinically relevant differences in serum creatinine between the two. No differences in adverse events. A potential source of bias is the fact that 50% of patients did receive 500 mL or more of saline in the balanced fluids group, which could have attenuated any real benefit of balanced fluids. Notably, a new systematic review (Jan 2022 NEJM Evidence), including this trial data, and suggests that there’s a high probability that, on average, balanced crystalloids reduce mortality. 

Bottom Line: Overall, this study did not find evidence of a benefit of Plasma Lyte over normal saline on all-cause mortality at 90 days. 

Additional Reading: 

• New Systematic review (Jan 2022, NEJM Evidence) comparing balanced crystalloid versus saline.  
• Check out the Fluid Wars episode #143 with @kidneyboy Joel Topf for more of a deep dive into these fluids. NephJC coverage of the BaSICS trial Jan 2021

Hot Takes

A brief discussion of recent articles, medical news, guidelines

Sleep and Energy Intake (Paul)

Tasali E et al. Effect of Sleep Extension on Objectively Assessed Energy Intake Among Adults With Overweight in Real-life Settings: A Randomized Clinical Trial. JAMA Intern Med. 2022 Feb 7. doi: 10.1001/jamainternmed.2021.8098. Epub ahead of print. PMID: 35129580.

Summary: What are the effects of a sleep extension intervention on energy intake, energy expenditure, and body weight in persons with overweight who habitually curtail their sleep duration? Obviously, I am (Paul) motivated by pure selfishness, and we have covered in some detail the problems of insufficient sleep. However, even though the measurement techniques were bananas, the intervention was achievable.  Eighty-one patients were randomized to a personalized sleep hygiene counseling session or instructed to continue their habitual sleep patterns after two weeks of their usual sleeping habits. Sleep duration was assessed by actigraphy, total energy expenditures were measured by the doubly labeled water method, and energy stores were calculated using weights and composition changes by dual-energy xray absorptiometry.

Bottom line: Sleep duration was increased by 1.2 hours per night in the extension group, who also consumed less energy (~270 Kcals/day) and had an average weight loss of 0.48 kg from their baseline. Participants in the control group had an average 0.39 kg weight gain.

Paul’s thoughts: I wonder how much of the change in weight and energy intake was due more to the counseling than the physiologic impact of sleep (e.g.,”Don’t eat right before bed”).  It was a small study done over a short period. So to me, this suggests counseling on sleep hygiene may be part of the toolkit when doing weight loss counseling.

New Vaccine Recs: PNA and HBV (Watto)

1. Kobayashi M et al. Use of 15-Valent Pneumococcal Conjugate Vaccine and 20-Valent Pneumococcal Conjugate Vaccine Among U.S. Adults: Updated Recommendations of the Advisory Committee on Immunization Practices — United States, 2022. MMWR. 2022;71(4);109–117.
2. Murthy N, et al; Advisory Committee on Immunization Practices†. Recommended Adult Immunization Schedule, United States, 2022. Ann Intern Med. 2022 Feb 18. doi: 10.7326/M22-0036. Epub ahead of print. PMID: 35175828.

Summary: 

• The PCV20 (20-valent pneumococcal conjugate vaccine) is now licensed for adults 18 years old and above to “maximize pneumococcal disease prevention among adults, reduce disparity, and simplify recommendations to improve vaccine uptake” [compared to PCV13 and PPSV23 combined regimen]. This recommendation comes despite some uncertainties about the significance of “lower immunogenicity” vs PCV13 and lack of coverage for some PPSV23 serotypes. Notably, “Shared decision-making” was removed. ACIP’s goal was to simplify recs for all groups.
• Universal hepatitis B virus (HBV) vaccination is now recommended for persons aged 19-59 years with goals to reduce infections by 90%, deaths by 65% and eliminate HBV by 2030 (AAFP News accessed 2/12/2022).

Bottom line: 

• Pneumococcal vaccine: Adults 65 and over (or 19-64 with comorbidities or immunocompromise) can now choose either PCV15 followed by PPSV23 in 1 year or a single PCV20 injection for PNA. 
• The Hepatitis B vaccine is now recommended for all adults 19-59 years old or those above 60 years old if at risk for infection or with comorbidities or immunocompromise.

Further reading: Medscape coverage 2/1/2022

Vitamin D & Autoimmune Disease (Rahul)

Hahn J, et al. Vitamin D and marine omega 3 fatty acid supplementation and incident autoimmune disease: VITAL randomized controlled trial. BMJ. 2022 Jan 26;376:e066452. doi: 10.1136/bmj-2021-066452. PMID: 35082139; PMCID: PMC8791065.

Question: Does daily vitamin D supplementation, with or without omega 3 supplementation, prevent the development of new autoimmune diseases among community-dwelling older adults? 

Comparison: Because this was a 2×2 factorial trial, there were four comparison groups: people randomized to daily vitamin D supplementation + placebo, daily omega 3 fatty acid supplementation + placebo, both vitamin D and the omega 3 together, or neither treatment (and both placebos). 

Results: Among 25,000 patients over a median of 5 years of follow-up, patients randomized to vitamin D, with or without omega 3s, experienced about a 20% relative reduction in the incidence of self-reported new autoimmune diseases of any kind. 

Bottom line: 

This was a technically positive study, but consider these two sources of chance and bias in applying these results: 

1. First, this was an ancillary study done as part of the VITAL trial (a trial designed to assess the impact of vitamin D and omega 3’s on the incidence of cancer and heart disease; this was a negative trial – results were published in NEJM in 2019). This is not dissimilar from doing multiple subgroup analyses within a single trial, which increases the likelihood of one of them yielding a positive result by chance alone – otherwise known as a type I error.
   1. How do we know that? By looking up the protocol! Just google the clinicaltrails.gov registry numbers at the end of the abstract. I do this when reading any randomized controlled trial.
2. Second, looking at the absolute risk reduction (ARR) helps put the results into perspective. Unfortunately, because the results are expressed as time-to-event, calculating this isn’t straightforward because everyone contributed different amounts of follow-up. So, I recommend using an online calculator like ClinCalc https://clincalc.com/Stats/NNT.aspx. To estimate ARR, we need to know the total number of patient-years of follow-up over which the outcomes occurred. This isn’t reported in the study, so here is how to estimate it: we know the study enrolled about 25,000 people with a median follow-up of about five years per patient. Multiplying them, we get 125,000 patient-years for the entire study. Assuming follow-up was equal in both groups, we divide by 2 and obtain 62,500 person-years for each group. From table 2, we see that 155 primary outcome events occurred in the control group, and 123 primary outcome events occurred in the vitamin D group (that is, 32 fewer events in the vitamin D group over 62,500 patient-years). Entering these into the calculator yields an ARR of about 0.03%, corresponding to a number needed to treat of ~2,700 people over five years. 
   1. These observations make me worry about one of two possibilities: either this is a false-positive result, such that there is either no real effect, or there is a real effect, but it is really, really small. 
3. To apply these results, you’d have to ask the question: is it worthwhile to treat more than 2,000 older adults for five years with vitamin D to prevent one autoimmune disease? Maybe, maybe not. This is not to say that vitamin D supplementation is without value – there may be other good reasons to use it, but based on this trial, I am not convinced that prevention of autoimmune disease alone is one of them.  

Ultrasound JVP tips (Watto)

Wang L et al. Accuracy of Ultrasound Jugular Venous Pressure Height in Predicting Central Venous Congestion. Ann Intern Med. 2021 Dec 28. doi: 10.7326/M21-2781. Epub ahead of print. PMID: 34958600.

Summary: POCUS uJVP was easily obtainable, reproducible, and accurately predicted CVP (quantitative uJVP had AUC 0.84 and qualitative uJVP was 94.6% specific for elevated CVP. Single-center, prospective observational study of 100 adult patients with heart failure comparing central venous pressure estimates with handheld POCUS (by two cardiology fellows, one cardiology attending) vs right heart catheterization. JVP was visualized in the transverse, NOT longitudinal orientation.

Bottom line: Perform a quantitative, reclined uJVP (measure with the patient lying at 30-45 degrees) or a qualitative (visualized or not) uJVP with the patient seated upright (feet on floor or legs extended in bed) as part of the volume status exam for heart failure…not to be interpreted in isolation.
See video from Annals site (top right of page) 

Links*

1. www.sumerton.com/concierge (The Novel Concierge)
2. Mozart in the Jungle (TV series)
3. Pull-up Bar 

Disco Elysium (Videogame)

*The Curbsiders participates in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising commissions by linking to Amazon. Simply put, if you click on our Amazon.com links and buy something we earn a (very) small commission, yet you don’t pay any extra.

Goals

Listeners will review recent practice-changing articles and medical news.

Learning objectives

After listening to this episode listeners will…

1. Recall that a balanced solution did not improve mortality compared to saline in the ICU
2. Discuss changes to the ACIP vaccine schedule for adults
3. Explain how sleep duration may affect energy intake
4. Utilize ultrasound to measure JVP
5. Decide whether or not Vitamin D and Omega-3s prevent autoimmune disease

Disclosures

The Curbsiders report no relevant financial disclosures. 

Citation

Taranto NP, Ganatra RB, Williams PN, Watto MF. “#325 Hotcakes: Fluid Wars revisited, Sleep & Weight Loss, Vitamin D, Pneumonia and HBV Vaccine Updates”. The Curbsiders Internal Medicine Podcast. http://thecurbsiders.com/episode-list Final publishing date March 7, 2022.