Saturday, October 11, 2014

Euboxia - Not Necessary (Or Necessarily Normal)

The Gist:  In medicine, we historically strive towards achieving values that fall within a reference range, or are normal, a phrase coined "euboxia" [1].  Targeting treatments to normalize values may not result in patient-oriented benefit and may cause harm.  We must also consider that normal values may not necessarily be normal for our patients.  Data fatigue, the exposure to copious data, may lead to ignoring values that are not flagged as abnormal, regardless of the appropriateness for a patient.
"'Euboxia' (from the Greek 'eu' meaning good, normal or happy, and 'box' from the tradition of writing physiological variables in boxes) is a colloquial word used in many North American and other hospitals to describe the state of apparent perfection aimed at by residents by the time they present their patients on morning rounds" - MC Meade [2].
Euboxia Is Not Always Necessary
Chris Nickson's Free Open Access Medical education (FOAM) post on Euboxia highlights some of the pitfalls with this obsession with normalcy. He also delivered a talk Euboxia and (ab)Normality at SMACC Gold which will hopefully be available on the SMACC podcast in the near future. A few examples include:
  • Hemoglobin transfusion trigger in anemia - Studies such as TRICC, CRIT, SOAP, and TRISS demonstrate that transfusion targets of more "normal" hemoglobin levels is not advantageous and may incur increased risks.  As such, transfusion triggers, in the absence of active myocardial ischemia, have moved to <7 g/dL while uptake of this trigger remains low in some communities [4]. 
  • Oxygen saturation in COPD - Unless patients are under duress, guidelines suggest patients with COPD have oxygen saturations targeted to 88-92% rather than the 98-100% more often associated with perfection [5]
  • Blood gas and saturations in ARDS - Guidelines for ventilation in patients with ARDS aim to protect the lungs using low tidal volumes and plateau pressures at the expense of allowing a pH of 7.20, permissive hypercapnia, and lower oxygen saturations of 88-95% (paO2 55-80 mmHg).  Correction of these lab abnormalities may come at the cost of additional lung damage by means of higher pressures or volumes and are thus discouraged [6].
Euboxia Is Not Necessarily Normal
Euboxia, however, may fool also practitioners into a false sense of security.  Failure to truly see a value that appears normal and isn't flagged, red, or outside of the box may be problematic. A few examples:

Normotension - Hypotension typically refers to systolic blood pressure <90 mmHg or a drop in systolic blood pressure >40 mmHg.  The latter part of this definition is often unable to be determined (due to lack of information) or forgotten.  The trauma literature seems to have solidified around the notion that the widely accepted definition of hypotension does not apply to many trauma patients, particularly those > 65 years old, and that 110 mmHg is probably a better cutoff [9-12].  While these recommendations have been out since 2011,  90 mmHg remains the common cut point for hypotension.
  • The CDC triage guidelines/"National Trauma Triage Protocol" have suggested <110 mmHg as the new hypotension guideline in patients > 65 years of age as multiple registry studies have demonstrated that an SBP <110 mmHg is associated with increased mortality and has an improved AUC compared with other blood pressure cut offs [9]. 
    • An abstract presented at AAST in 2014 found that patients >65 y/o with an SBP 90-109 mmHg had an odds of mortality of 9.7 (95% CI 8.7-10.8, p<0.01).  This survey study found improved, but terrible sensitivity for Trauma Center Need (ISS>15, ICU admit, urgent OR, or ED death) with the higher SBP cut-off [10].
Normal White Blood Cell Count (WBC) - Leukocytosis is often used as a predictor of infection/inflammation and historically loved by surgical services, yet the operating characteristics don't perform that well.  During a lecture as a medical student Dr. Sean Fox (PEM Morsels) shared the following perspective on the WBC, "WBC is the last bastion of the intellectually destitute."
I soon discovered that the sensitivity and specificity of leukocytosis, or the absence thereof, wasn't helpful in many situations.
  • In acute cholecystitis, for example, the WBC proves unhelpful as demonstrated by the following operating characteristics for leukocytosis: +LR 1.5; -LR 0.6; Sensitivity 63%; Specificity 57% [13].  Thus, a normal WBC does not help rule out acute cholecystitis.  Similarly, a normal WBC does not exclude acute appendicitis, although values <8 (a normal value) may have some utility in this regard according to Bundy et al.  
Normal Potassium in DKA - The reference range for potassium runs approximately 3.5-5 mEq/L.  Patients presenting in DKA may have low normal potassium concentrations but have severe total body potassium deficits.  As a result, professional societies recommend withholding insulin if a patient has a potassium <3.5 and supplementing potassium even when values are well within the upper "normal" limit of 4-5 mEq/L [14].  Despite these teachings and nearly habitual practice, without mindful attention to the potassium the "normal" lab value could easily be ignored. 

Normal Lactate - Lactate is beloved in Emergency Department (ED) care and it's well accepted that elevated lactate values predict mortality.  Yet, normal lactate levels may be falsely reassuring.  Lactate has been used as screening test in mesenteric ischemia as small, early reports yielded a sensitivity of 100% [15].  More recent analysis, however, show that the +LR 1.7 (1.4–2.1), -LR 0.2 (0–2.9) for L-lactate.  The -LR for lactate crosses 1.0, demonstrating that a normal lactate is not useful in crossing mesenteric ischemia off the list [16].  While we may cognitively understand this notion, in practice I think we quite often feel reassured by normal lactates (or reassure the admitting teams).

What to do?
Data overload and obsession may engender a sort of "data fatigue."  It is difficult to notice abnormalcy in data that may appear, for most individuals, normal.  This may be particularly arduous in a sea of numbers.  Furthermore, our attention is typically drawn to the red or flagged "abnormal" numbers.  This is not to suggest that we should agonize over every value and cannot trust anything "normal."  Rather, it seems that the signal in medicine is that tests and parameters are only as good as the context of the patient and the provider interpreting them. Here's what I'm trying, to combat my own data fatigue and subconscious euboxic thinking:
  • Think about a patient's clinical context, which requires mindfulness in the fast pace and overwhelming environment we call an ED.
  • Order a test?  Review the results (really), paying attention and process the results in the context of the patient.
  • If possible and appropriate, prevent data overload and data fatigue by ordering tests that will add value to the care of the patient.
References:
1.  Reade MC. The pursuit of oxygen euboxia. Anaesth Intensive Care. 2013;41(4):453–5.
2.  Reade MC. Should we question if something works just because we don’t know how it works? Crit Care Resusc. 2009;11(4):235–6. 
3. Nickson CN.  Don't Put Your Patient In A Box.  Life in the Fast Lane. 
4. Carson JL, Grossman BJ, Kleinman S et al.  Red blood cell transfusion: a clinical practice guideline from the AABB.*Ann Intern Med. 2012 Jul 3;157(1):49-58.
5. Abdo WF, Heunks LM. Oxygen-induced hypercapnia in COPD: myths and facts. Crit Care. 2012 Oct 29;16(5):323. 
6.The Acute Respiratory Distress Syndrome Network (2000) Ventilation with low volumes as compared with traditional tidal volumes for acute lung injury and acute respiratory distress syndrome. N Engl J Med 342:1301-1308 
7. Putensen C, Theuerkauf N, Zinserling J et al. Meta-analysis: ventilation strategies and outcomes of the acute respiratory distress syndrome and acute lung injury. Ann Intern Med. 2009 Oct 20;151(8):566-76.
10. Brown JB, Gestring ML, Forsythe RM et al. Systolic Blood PRessure Criteria in the National Trauma Triage Protocol for Geriatric Trauma: 110 is the new 90.  Oral Abstracts, AAST July 2014.
11. Eastridge BJ, Salinas J, McManus JG, et al. Hypotension begins at 110 mm Hg: redefining “hypotension” with data. J Trauma. 2007;63(2):291–7; discussion 297–9.
12. Oyetunji TA, Chang DC, Crompton JG, et al. Redefining hypotension in the elderly: normotension is not reassuringArch Surg. 2011;146(7):865–9.
13. Trowbridge RL, Rutkowski NK, Shojania KG. Does This Patient Have Acute Cholecystitis? JAMA. 2003;289(1):80–86.
14. Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009;32(7):1335–43. 
15. Lange H, J├Ąckel R. Usefulness of plasma lactate concentration in the diagnosis of acute abdominal disease. Eur J Surg. 1994;160(6-7):381.
16.  Cohn B.  Does This Patient Have Acute Mesenteric Ischemia?  Ann Emerg Med. 2014 Jan 30

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