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This is an exciting week of primary literature, particularly as many large critical care trials were published in major journals despite being “negative studies.”  We are excited by this as, too often, we see “negative studies” discarded.  Further, these studies examined things some practices we seem to believe in: balanced crystalloids, apneic oxygenation (see Dr. Scott Weingart’s podcast on the FELLOW study), treating fever. We love that the Free Open Access Medical Education (FOAM) community and study authors are examining beloved practice and open to questioning the very things we believe in. Well done.

We cover two core content papers out by Dr. Paul Young (@dogICUma) in JAMA and NEJM this week. His trials are as clever as his Twitter handle.

SPLIT – The FOAM world has sung the praises of balanced fluids given they have more physiologic composition. The thought, as detailed in this post, is that 0.9% NaCl contains an ABnormally large amount of chloride which may cause a hyperchloremic metabolic acidosis. Prior literature suggests an increased incidence of kidney injury with saline compared with balanced solutions. Thus, Dr. Paul Young and colleagues sought to study this with the best trial, to date, on this topic.

• Multicenter, blinded,  cluster-randomized, double-crossover trial of adult ICU patients receiving crystalloids randomizing patients to 0.9%NaCl or Plasma-lyte (balanced solution).
  • Sites used one fluid for seven weeks and then crossed over to the other fluid (labeled Fluids A and B).
• Primary outcome: AKI according to the RIFLE criteria  within 90 days – no difference between groups.
  • 9.6% in Plasma-lyte group vs 9.2% in the saline group (absolute difference 0.4% [95% CI, −2.1%-2.9%]; RR, 1.04 [95% CI, 0.80-1.36]; P = .77)
• Secondary outcomes: No difference in renal replacement therapy, ICU days, mechanical ventilation, or mortality
• A few things to keep in mind:
  • 70% of patients were admitted to the ICU from the OR (mostly cardiac surgery) and only ~15% from the ED
  • Patients got a median of 2L (1L -3.5L) of the study fluid, that’s it. These were not large volume resuscitations.
  • 90% of patients received fluids prior to enrollment, 60% got balanced crystalloid and only 30% 0.9% NaCl.

HEAT – We can’t help treating fever. We like the numbers euboxic, elevated temp? It must be bad! Doctors, parents, nurses treat fever reflexively.  Yet, there’s a thought that fever may be evolutionary and could potentially be protective. Treating pain or discomfort? That’s one thing, but here the authors sought to determine if there was a clinically important benefit to treating the number in ICU patients.

• Randomised controlled, double blinded study of n=690 ICU patients with T>38F + suspected infection randomized to receive either 1 g paracetamol (acetaminophen/APAP) or placebo every 6 hours.
• Primary outcome: median ICU-free days to day 28 – no difference 23 (IQR 13-25) in paracetamol group vs 22 in placebo group (IQR 12-25); P=0.07
• No difference in secondary outcomes of mortality at 28 and 90 days
• Limitations: ~30% of patients in both arms received open label APAP after the course of the study drug

Bottom Line Pearls:

• It appears we may be SPLITting hairs over fluid choices. Giving a couple of liters? Fluid choice may not matter. SPLIT does not provide literature for larger volume resuscitations.
• Treating fever in ICU patients with suspected infection doesn’t have an effect on ICU free days. Treat discomfort and pain with APAP but don’t expect to save lives or ICU beds by doing so.
• “Negative studies” are important. So is examining our practice.

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We are bringing you pearls from conferences we attend including SMACC (#smaccUS).  The plenary, facilitated by the brilliant Dr. Victoria Brazil, focused on the impaired provider. At SMACC we’ve heard time and time again – we are fallible, we make mistakes.

Dying – Dr. Ashley Shreves

• What often presume what our patients want without asking them.  When dying patients are asked what they want, it comes down to dignity. 1) Being clean 2) Naming a decision maker and then other top priorities essentially come down to healthcare providers listening [Steinhauser et al]
• We don’t ask patients about their code statuses appropriately. First, we often spend almost no time doing this.  One study of hospitalists found that code status discussions lasted, on average, one minute. Further, that one minute was spent mostly focused on procedures [Anderson et al]
• Communicate!

Evidence Based Medicine – The consensus of these cage matches was that evidence isn’t all equal; the existence of data doesn’t necessarily mean it’s good data.

• The Randomized Control Trial (RCT) has problems – Drs. Paul Young and Simon Finfer
  • Beware the Fragility Index – small effects in RCTs
  • Caution with Base Rate Neglect – we jump to inappropriate conclusions.  For example, pretend you have tested positive for a typically fatal disease.  The test is accurate 95% of the time.  Most people would conclude that there was a 95% chance they have the disease – a death sentence. Yet, one would need to know the prevalence of the disease in the general population to determine the actual likelihood that the test was correct.  If the prevalence of the disease is 1 in 1000, the likelihood that you actually have the disease based on this test is <2%.
• We should read the primary literature, but we can’t read all of it. Use FOAM (judiciously) – Drs. Rory Spiegel and Ken Milne
  • Due to the volume of literature, we have to make some decisions on what to read (Systematic reviews? Meta-analyses? RCTs? Case Reports?)

Impact Apnea

• Severe traumatic brain injury can cause apnea which leads to a spiral of hypoxia (and thus cell death) and hypercapnea (with cerebral vasodilation causing cerebral edema) which can result in poor neurologic outcome.
• The key?  Resuscitate these patients as a hypoxic arrest. These are patients that need an airway and need oxygen.

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The Free Open Access Medical Education (FOAM)

This week we cover Dr. Scott Weingart’s EMCrit episode on Thyroid Storm

Diagnosis: Hyperthyroid, Fever, Altered Mental Status, Sympathetic Surge, Precipitating Event

• Use the Burch-Wartofsky scoring system

Treatment (PPID – PTU, propranolol, iodine, dexamethasone or MIEH – methimazole, iodine, esmolol, hydrocortisone):

• Supportive care – IV fluids, identify trigger (infection, DKA, trauma, etc)
• Block production of thyroid hormone: Methimazole or Propothiouracil (PTU)
• Block thyroid hormone release: Iodine (wait 60 min after giving methimazole or PTU)
• Calm the sympathetic surge: beta-blockade (propranolol – also inhibits conversion of T4 to the more active T3, metoprolol or esmolol)
• Block conversion of T4 to T3 and prevent adrenal insufficiency: steroids (dexamethasone, hydrocortisone)

Core Content
Rosen’s Emergency Medicine (8e) Chapter 128, Tintinalli (7e) Chapter 223

Thyroid disorders exist on a spectrum from myxedema coma to thyroid storm, with a large area in between.

Hyperthyroidism – too much thyroid hormones only from the thyroid gland

Thyrotoxicosis –  too much thyroid hormone from any cause (i.e. taking too much thyroid supplement)

Thyroid Storm – see above. Thyrotoxicosis with  increased adrenergic hyperactivity or abnormal response to the thyroid hormones by the peripheral tissues

Myxedema coma – These patients are the opposite of thyroid storm, all the systems are depressed (they are essentially hypo-everything).  The diagnosis is clinical but these patients will have significantly elevated TSH with low T3/T4.

• Altered mental status
• Hypothermic, <35.5°C (95.9°F)
• Hypotensive
• Bradycardic
• Hyponatremic
• Hypoglycemic

Treatment –

• Intravenous levothyroxine (T4) although endocrine may recommend that some patients get intravenous T3
• Supportive care – passive rewarming, dextrose, intravenous fluids
• Steroids
• Identify underlying cause

Generously Donated Rosh Review Questions 

1. A 28-year-old woman with no past medical history presents to the emergency department with acute dyspnea. Physical exam reveals tachycardia, warm extremities, wide-pulse pressure, bounding pulses, a systolic flow murmur, exophthalmos and a neck mass. [polldaddy poll=8935230]

2. [polldaddy poll=8936552]

Answers

1. This patient most likely has high-output heart failure secondary to thyrotoxicosis. High output heart failure occurs when cardiac output is elevated in patients with reduced systemic vascular resistance. Examples include thyrotoxicosis, anemia, pregnancy, beriberi and Paget’s disease. Patients with high output heart failure usually have normal pump function, but it is not adequate to meet the high metabolic demands. In high output heart failure the heart rate is typically elevated, the pulse is usually bounding and the pulse pressure wide. Pistol-shot sounds may be auscultated over the femoral arteries, which is referred to as Traube’s sign. Subungual capillary pulsations, often referred to as Quincke’s pulse, may be also be present. Although these findings may be seen in other cardiac conditions, such as aortic regurgitation or patent ductus arteriosus, in the absence of those conditions, these signs are highly suggestive of elevated left ventricular stroke volume due to a hyperdynamic state. Patients with chronic high output also may develop signs and symptoms classically associated with the more common low-output heart failure; specifically, they may develop pulmonary or systemic venous congestion or both, while maintaining the above normal cardiac output.

Low output heart failure (C) is often secondary to ischemic heart disease, hypertension, dilated cardiomyopathy, valvular and pericardial disease or arrhythmia. It can cause dyspnea but is not associated with symptoms of a hyperdyanmic state. Aortic regurgitation (A) is classically associated with bounding pulses, a wide pulse pressure and subungual capillary pulsations; however, aortic regurgitation is less likely in a young woman with no past cardiac history. Additionally, this woman has exophthalmos and a goiter on exam, which support the diagnosis of thyrotoxicosis. Methamphetamine intoxication (D) usually presents with agitation, tachycardia, and psychosis; however, it is not associated with a hyperdynamic state, exophthalmos or a goiter.

2.  Hyperthyroidism is a condition in which there is overproduction and increased circulation of thyroid hormone. Hyperthyroidism has a variety of causes and variable presentation. Increased circulating thyroid hormone causes a hypermetabolic state and increases beta-adrenergic activity. Initially, patients may have vague constitutional symptoms. As the disease progresses, clinical manifestations may become more organ-specific. Thyrotoxicosis or thyroid storm represents the most severe manifestation of the disease. Thyroid storm is life threatening and characterized by hyperadrenergic activity. Patients present with vital sign abnormalities including tachypnea, tachycardia, hyperthermia and hypertension. ECG may show atrial dysrhythmias like atrial flutter and fibrillation or simple sinus tachycardia. High-output cardiac failure is common as well. Physical features include goiter, opthalmopathy and tremors. Patients will also have increased reflexes and altered mental status. Thyroid storm treatment involves suppression of thyroid hormone synthesis and secretion, prevention of peripheral conversion from T4 to T3 and blocking the peripheral adrenergic stimulation. Blocking the peripheral effects of thyroid hormone is best accomplished with a beta-blocker and propranolol is preferred as it also decreases conversion of T4 to T3.

Lithium (A) is a cause of hypothyroidism. In hyperthyroidism, TSH is depressed (C). Weight gain (D) is common in hypothyroidism.

Theme Music:  Flippen performed by The Punch Brothers, used with permission