#195 TWDFNR 3: Potassium, Oxygen, and Antipsychotics

February 17, 2020 | By Justin Berk

Why Chasing the K+ should not drive you bananas, extra oxygen should not give you comfort, and avoiding antipsychotics for delirium should not be confusing

Discover common practices that persist in the hospital wards despite no proven benefit! We review how potassium replacement goals should not drive you bananas, extra oxygen should not give you comfort, and how you should maybe calm down with antipsychotics for delirium. Join returning guests: high-value care specialist Dr. Lenny Feldman (@DocLennyF, Johns Hopkins) and tweetorialist Dr. Tony Breu (@tony_breu, Harvard) as they walk us through round 3 of “Things We Do for No Reason^TM (TWDFNR 3).

SHM members can claim CME-MOC credit at https://www.shmlearningportal.org/curbsiders (CME goes live at 0900 ET on the episode’s release date). Note: The planners and faculty for this activity have no relevant relationships or conflicts to disclose.

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Credits

Written and Produced by: Burton H. Shen MD, Justin Berk, MD MPH MBA

Infographic:

Cover Art:

Hosts: Justin Berk MD MPH MBA; Stuart Brigham MD; Matthew Watto MD, FACP; Paul Williams MD, FaCP

Editor: Matthew Watto MD, FACP (written materials); Clair Morgan of Nodderly.com (audio)

Guest: Lenny Feldman MD, Tony Breu MD

Sponsors

Hospital Medicine 2020 (HM20) is the Society of Hospital Medicine’s Annual Conference April 15th through the 18th in sunny San Diego. Don’t miss the largest hospital medicine meeting. Register now at https://shmannualconference.org/ and use the code CURBSIDERS to receive a $50 discount.

Time Stamps

• 00:00 Sponsors –SHM’s Annual Conference, HM20 (use code CURBSIDERS) and Primary Care Internal Medicine of Ithaca (email: arcostello@gmail.com)
• 00:38 Intro, disclaimer, guest bio
• 02:10 Guest one-liners
• 03:35 Picks of the Week*: Knives Out (film), Priced Out by Uwe E. Reinhardt; Crisis in the Red Zone by Richard Preston; CardioNerds podcast; Outbreak (film); Teaching Physiology on the Fly (faculty development course)
• 07:55 Sponsors –SHM’s Annual Conference, HM20 (use code CURBSIDERS) and Primary Care Internal Medicine of Ithaca (email: arcostello@gmail.com)
• 09:30 Case of Eric Lokay; Repleting potassium. Is it necessary to “buff the lytes”
• 20:30 Pathophysiology of hypokalemia; Final recommendations on potassium repletion
• 24:30 Supplemental oxygen; pO2 vs total oxygen content; Oxygen, vasoconstriction and potential harms
• 30:33 Evidence of harm from supplemental O2
• 35:00 Tony’s recommendations for use of supplemental O2
• 41:55 Case of delirium; Definition and diagnosis
• 46:20 Can we prevent delirium? Melatonin and ramelteon
• 50:33 Should we use antipsychotics? Benzodiazepines?; What should we do instead?
• 58:25 Take home points, Outro and a terrible pun

TWDFNR 3 – Pearls

1. For patients with acute MI, acute decompensated heart failure, or critical care patients, there is no evidence for a potassium goal above 4.0. A reasonable potassium goal may be 3.5 to 4.5.
2. Oxygen is a medication with benefits but also significant side effects.
3. Supplemental oxygen for patients with >90% O2 saturation or >88% for COPD patients may be harmful rather than helpful. 
4. For delirious patients, medications do not offer benefit and may cause side effects. Non-pharmacologic methods are first-line therapies.  

Things We Do for No Reason^TM Show Notes

The History of Things We Do For No Reason^TM (TWDFNR)

Started in 2012 at SHM Annual Meeting, “Things We Do For No Reason™” was a talk that covered 3 – 4 new topics each year representing “the low hanging fruit of high value care.”  Topics include practices that have no evidence behind them, don’t help patients, and are things we should, for the most part, get rid of. These topics have now become a regular series in the Journal of Hospital Medicine.  The goal is for learners to become more skeptical and question norms rather than accept practices without evidence.

Check out this Master Index with all the Choosing Wisely / TWDFNR articles!

Potassium Replacement “Buffing the Lytes”

TWDFNR Article – Potassium Replacement (publication pending)

What is a normal potassium level?

Dr. Feldman’s expert opinion: 3.5-5.0 mEq/L

European Resuscitation Council Guidelines in 2015 said there is no universal definition for hyperkalemia. They defined hypokalemia as <3.5 and hyperkalemia as >5.5

Current Guidelines for Electrolyte Replacement for Patients with Myocardial Infarction

There are not great guidelines for electrolyte replacement patients who present with an acute myocardial infarction, despite being almost universally taught, that acute MI patients should have potassium level greater than 4.0. 2017 AHA/ACC/HRS guidelines centered around preventing ventricular fibrillation or ventricular tachycardia with a “normal” potassium level. 

Where does the goal of 4.0 come from?

Studies that have looked at admission potassium level showed increased risk of ventricular arrhythmias if the admission potassium was low [Patel 2017].  

The National Council on Potassium in Clinical Practice recommends a target of 4.0 or higher in patients with heart disease who are at risk for serious ventricular tachyarrhythmias [Cohn, 2000]. No major organizations clearly state what the goal should be after an acute MI. 

What’s the risk of “potassium buffing”?

Potentially, death. Dr. Feldman shared an anecdote of having a patient die when he was replacing potassium (intravenously) for a potassium under 4. 

What’s the latest data on potassium replacement?

A retrospective observational study that looked at admission and mean potassiums for about 38,000 patients with acute MI from 2000 to 2008 across 67 hospitals. The end points were arrhythmias AND mortality. They found that mean potassium levels between 3.5 and 4.0 had the lowest mortality. Mean potassium below 3.5 was associated with increased mortality and mean potassium above 4.5 was also associated with increased mortality [Goyal, 2012].

Dr. Breu’s expert opinion: Low potassium could cause arrhythmias, but could also be a confounder. Low potassium could indicate high levels of catecholamines that might be causing the arrhythmia, rather than the low potassium being the cause.

Goyal, 2012

What should the threshold be to give potassium replacement for hospital patients?

Dr. Feldman’s expert opinion: Patients with acute MI with a potassium between 3.0 to 3.5 should receive potassium replacement. Based on observational data, potassium of 3.5-4.0 is a good goal. Do not try to push K+ above 4.4. For other internal medicine patients, 3.5-4.0 seems to be a reasonable goal, but this is all based on observational data.

Dr. Breu’s expert opinion: For patients with acute MI, acute heart failure, and cirrhosis at risk for hepatic encephalopathy, the goal is over 3.5; otherwise, patients with potassium over 3.0 is acceptable. 

Supplemental Oxygen

TWDFNR Article – Supplemental Oxygen

How does supplemental oxygen affect oxygen delivery to tissue?

As supplemental O2 increases for patients, it increases pO2 well, but does not increase total oxygen content. If pO2 increases from 100 to 500 mm Hg, the total oxygen content has increased only 6%. Even though pO2 goes up by five times, the actual content increases only 6%. Increasing supplemental does not increase oxygen to the tissues by that much. The sensors in the body react to pO2, not total oxygen content [Loscalzo, 2017].

When pO2 increases, the reaction by the vessels (with the exception of the lungs) is to vasoconstrict because oxygen free radicals are toxic. The body vasoconstricts to protect the tissue from the free radicals of oxygen. This decreases the delivery of blood to the tissues [Collins, 2015].

What’s the evidence for oxygen causing harm?

James Lorrain Smith put birds in chambers with increasing oxygen content that showed the toxic effects of oxygen [Smith, 1899]. Dr. Breu cited multiple studies from the 1940s that show increased oxygen causes vasoconstriction of the arteries feeding the brain and the coronary arteries. 

What’s the evidence for oxygen causing harm in human patients?

A randomized control trial (by the AVOID investigators) looked at patients with a myocardial infarction with an O2 saturation of 94% and randomized them to either eight liters of supplemental oxygen or no supplemental oxygen. The patients randomized to the supplemental oxygen group had an increased risk of recurrent MI and a larger infarct size [Stub, 2015].

The IOTA systematic review and meta-analysis, found that acutely ill patients with O2 saturations above 96% had increased in-hospital mortality [Chu, 2018].

Patients who have acute COPD exacerbation are at risk of becoming hypercarbic. The physiology is often cited as the “loss of hypoxic drive,” which plays a role, but according to Dr. Breu, it is likely the loss of hypoxic vasoconstriction in the lung that probably contributes more to the hypercarbia.

“Worsening ventilation-perfusion matching and the Haldane effect (decreased affinity of hemoglobin for carbon dioxide as the PaO2 rises), rather than the previously theorized decrease in hypoxic drive, are now believed to contribute most to hyperoxia-induced hypercarbia.” –TWDFNR (Moss, 2019)

What are the recommendations for supplemental oxygen? 

Per the BMJ Practice Recommendations: the strongest recommendations are for patients with acute MI and acute stroke. Do not give supplemental oxygen if O2 saturation is above 92% (strong recommendation) or above 90% (weak recommendation). For all other patients, there is no recommendation for a lower limit, but stop or turn down supplemental oxygen for oxygen saturation over 96% [Siemieniuk, 2018].

Dr. Breu’s expert opinion: Do not start supplemental oxygen for patients with >90% O2 saturation or >88% for COPD patients. Turn down or stop supplemental oxygen for O2 saturation over 96%. 

Antipsychotics for Delirium

TWDFNR Article – Antipsychotics for Delirium 

Definition of Delirium

Delirium is an acute change in cognition that is almost always characterized by inattention, and typically associated with disordered thinking and/or alterations in consciousness. 

How do you diagnose delirium?

Dr. Feldman suggests that the pre-test probability for delirium for admitted patients is about 33%. He recommends asking “what day of the week is it?” and asking the patients to recite the months backwards. These are tests with good sensitivity (93%)[Fick 2015].  Another test developed for diagnosing delirium is the 3D-CAM test [Marcantonio, 2014].

What medications can prevent delirium?

For prevention of delirium, there are no good medications that have been shown to help prevent delirium, except for maybe melatonin or melatonin agonists [Nishikimi, 2018, Siddiqi, 2016, Ng, 2020]. 

What medications can treat delirium?

Not benzodiazepines (unless the patient is in alcohol withdrawal), not acetylcholinesterase inhibitors, and not antipsychotics based on the larger meta-analyses [Lonergan, 2009, Yu, 2018, Burry, 2018]. A few studies have shown some positive results from antipsychotics quetiapine and haloperidol, but the data is not strong [Tahir, 2010, Kalisvaart, 2005].

“The prescribing practitioner should not prescribe antipsychotic… medications for the treatment of older adults with postoperative delirium who are not agitated and threatening substantial harm to self or others.”

The American Society of Geriatrics https://www.ncbi.nlm.nih.gov/pubmed/25495432

What can be done for delirium?

Dr. Feldman’s expert opinion: Remove IVs if they are not needed. If they need the IV, tape the tubing with gauze from the wrist to the shoulder and have the attached tubing exit behind the shoulder. Don’t draw blood if you don’t need to. Don’t take vital signs if you don’t need to. Get rid of problematic medications. Correct any metabolic disturbances. Let the patient sleep. Get them private rooms to help them sleep. Get the patients mobile. Treat pain if applicable. 

Goal

Listeners will be able to explain the target potassium levels for patients with acute MI and acute heart failure, target goals for O2 saturation, and the evidence of why antipsychotics do not work well for delirium. 

Learning objectives

After listening to this episode listeners will…  

1. Be familiar with the indications for potassium replacement. 
2. Describe the goal range for potassium. 
3. Recall the basic pathophysiology oxygen saturation.  
4. Recognize the potential harm of oxygen. 
5. Describe goal oxygen saturation for different patient populations. 
6. Recognize the importance of preventing delirium and different methods to prevent delirium. 

Links*

1. Knives Out (film)
2. Priced Out by Uwe E. Reinhardt
3. Crisis in the Red Zone by Richard Preston
4. CardioNerds podcast
5. Outbreak (film)
6. Teaching Physiology on the Fly (faculty development course)

*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.

References

1. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: Executive summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Heart Rhythm. Oct 2018;15(10):e190-e252. https://www.ncbi.nlm.nih.gov/pubmed/29097320 
2. American Geriatrics Society Expert Panel on Postoperative Delirium in Older A. American Geriatrics Society abstracted clinical practice guideline for postoperative delirium in older adults. J Am Geriatr Soc. Jan 2015;63(1):142-150. https://www.ncbi.nlm.nih.gov/pubmed/25495432 
3. Burry L, Mehta S, Perreault MM, et al. Antipsychotics for treatment of delirium in hospitalised non-ICU patients. Cochrane Database Syst Rev. Jun 18 2018;6:CD005594. https://www.ncbi.nlm.nih.gov/pubmed/29920656 
4. Chu DK, Kim LH, Young PJ, et al. Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis. Lancet. Apr 28 2018;391(10131):1693-1705. https://www.ncbi.nlm.nih.gov/pubmed/29726345 
5. Cohn JN, Kowey PR, Whelton PK, Prisant LM. New guidelines for potassium replacement in clinical practice: a contemporary review by the National Council on Potassium in Clinical Practice. Arch Intern Med. Sep 11 2000;160(16):2429-2436. https://www.ncbi.nlm.nih.gov/pubmed/10979053 
6. Collins JA, Rudenski A, Gibson J, Howard L, O’Driscoll R. Relating oxygen partial pressure, saturation and content: the haemoglobin-oxygen dissociation curve. Breathe (Sheff). Sep 2015;11(3):194-201. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4666443/ 
7. Dudum R, Lahti SJ, Blaha MJ. High-Goal ‘Lytes: Repletion Gone Awry? J Hosp Med. Dec 1 2019;14(12):785-786. https://www.journalofhospitalmedicine.com/jhospmed/article/204969/hospital-medicine/high-goal-lytes-repletion-gone-awry 
8. Goyal A, Spertus JA, Gosch K, et al. Serum potassium levels and mortality in acute myocardial infarction. JAMA. Jan 11 2012;307(2):157-164. https://www.ncbi.nlm.nih.gov/pubmed/31339839 
9. Kalisvaart KJ, de Jonghe JF, Bogaards MJ, et al. Haloperidol prophylaxis for elderly hip-surgery patients at risk for delirium: a randomized placebo-controlled study. J Am Geriatr Soc. Oct 2005;53(10):1658-1666. https://www.ncbi.nlm.nih.gov/pubmed/16181163 
10. Lonergan E, Luxenberg J, Areosa Sastre A. Benzodiazepines for delirium. Cochrane Database Syst Rev. Oct 7 2009(4):CD006379. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6669269/ 
11. Loscalzo J. Is Oxygen Therapy Beneficial in Acute Myocardial Infarction? Simple Question, Complicated Mechanism, Simple Answer. N Engl J Med. Sep 28 2017;377(13):1286-1287. https://www.ncbi.nlm.nih.gov/pubmed/28844195 
12. Marcantonio ER, Ngo LH, O’Connor M, et al. 3D-CAM: derivation and validation of a 3-minute diagnostic interview for CAM-defined delirium: a cross-sectional diagnostic test study. Annals of internal medicine. Oct 21 2014;161(8):554-561. https://www.ncbi.nlm.nih.gov/pubmed/25329203 
13. Monsieurs KG, Nolan JP, Bossaert LL, et al. European Resuscitation Council Guidelines for Resuscitation 2015: Section 1. Executive summary. Resuscitation. Oct 2015;95:1-80. https://www.ncbi.nlm.nih.gov/pubmed/26477410 
14. Moss BJ, Sargsyan Z. Things We Do For No Reason: Supplemental Oxygen for Patients without Hypoxemia. J Hosp Med. Oct 23 2019;14:E1-E3. https://www.ncbi.nlm.nih.gov/pubmed/31634107 
15. Ng KT, Teoh WY, Khor AJ. The effect of melatonin on delirium in hospitalised patients: A systematic review and meta-analyses with trial sequential analysis. J Clin Anesth. Feb 2020;59:74-81. https://www.ncbi.nlm.nih.gov/pubmed/31279283 
16. Nishikimi M, Numaguchi A, Takahashi K, et al. Effect of Administration of Ramelteon, a Melatonin Receptor Agonist, on the Duration of Stay in the ICU: A Single-Center Randomized Placebo-Controlled Trial. Crit Care Med. Jul 2018;46(7):1099-1105. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6012040/ 
17. Pahwa AK, Qureshi I, Cumbler E. Things We Do For No Reason: Use of Antipsychotic Medications in Patients with Delirium. J Hosp Med. Mar 20 2019;14:E1-E3. https://www.ncbi.nlm.nih.gov/pubmed/30897059 
18. Siddiqi N, Harrison JK, Clegg A, et al. Interventions for preventing delirium in hospitalised non-ICU patients. Cochrane Database Syst Rev. Mar 11 2016;3:CD005563. https://www.ncbi.nlm.nih.gov/pubmed/26967259 
19. Siemieniuk RAC, Chu DK, Kim LH, et al. Oxygen therapy for acutely ill medical patients: a clinical practice guideline. BMJ. Oct 24 2018;363:k4169. https://www.ncbi.nlm.nih.gov/pubmed/30355567 
20. Smith JL. The pathological effects due to increase of oxygen tension in the air breathed. J Physiol. Mar 22 1899;24(1):19-35. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1516623/ 
21. Stub D, Smith K, Bernard S, et al. Air Versus Oxygen in ST-Segment-Elevation Myocardial Infarction. Circulation. Jun 16 2015;131(24):2143-2150. https://www.ncbi.nlm.nih.gov/pubmed/26002889 
22. Tahir TA, Eeles E, Karapareddy V, et al. A randomized controlled trial of quetiapine versus placebo in the treatment of delirium. J Psychosom Res. Nov 2010;69(5):485-490. https://www.ncbi.nlm.nih.gov/pubmed/20955868 
23. Yu A, Wu S, Zhang Z, et al. Cholinesterase inhibitors for the treatment of delirium in non-ICU settings. Cochrane Database Syst Rev. Jun 28 2018;6:CD012494. https://www.ncbi.nlm.nih.gov/pubmed/29952000 

Disclosures

Dr. Feldman and Dr. Breu report no relevant financial disclosures. The Curbsiders report no relevant financial disclosures. 

Citation

Feldman L, Breu T, Shen BH, Berk JL, Williams PN, Brigham SK, Watto MF. “#195 TWDFNR^TM 3: Potassium, Oxygen, and antipsychotics”. The Curbsiders Internal Medicine Podcast. http://thecurbsiders.com/episode-list. February 17, 2020.