POTD. Myxedema Coma.

A nice week of spring fling came and went. in honor of the return of the cold. lets have a discu-shin about an uncommon, but deadly cause of hypothyroidism - myxedema coma. 

• Why do I care?

  • because mortality rates in treated MC approach 60%

    • if missed and untreated, mortality approaches 100%. 

• How does it present?

  • Severe hypothyroidism --> everything slows down. hypothermia and decreased mental status are hallmarks, other common signs are hypotension, bradycardia, hyponatremia, hypoventilation, and hypoglycemia. 

    • interestingly, it is aka myxedema madness - as sometimes patients present with psychosis. 

    • due to its rarity it can be a confusing Ddx - think of a patient with multiple failing organs whose lethargic, hypotensive, and hypothermic

    • ddx include sepsis, CHF, tox, adrenal crisis

    • to make things more complicated, myxedema coma usually occurs in a patient with hypothyroidism as a result of a precipitant

    • any systemic insult can push a patient in to myxedema (overdose, CHF, CVA, sepsis, trauma, etc.)

• so youre saying the differential diagnosis can actually be the cause?

  • YES I AM

• So how will i recognize it????

  • You'll send a thyroid panel to the lab

  • and you'll realize that your standard treatments for whatever else may be present just are not working as well as you'd expect them to. 

    • BP will not respond to pressors as well you'd expect. 

• How do I treat it?

  • controversial. most agree to adminster both T3 and T4 (levothyroxine)

    • T4: 4mcg/kg IV

      • followed by 75-100 mcg daily IV until patient tolerates PO

    • T3: 10mcg IV

      • followed by 2.5-10 mcg IV daily

  • concomitant adrenal insufficicnecy may be present

    • administer hydrocortisone 100 IV q8

• where should i send this patient?

  • to the MICU. and get your endocrinologists involved. 

Pressors in cardiogenic shock

“Pressors” in Cardiogenic Shock in adults

• Vasopressors- Pure vasoconstriction without any inotropy eg Phenylephrine and Vasopressin

• Inotrope- Increase cardiac contractility à improving SV and cardiac output without any vasoconstriction eg Milrinone

• Inopressors - a combination of vasopressors and inotropes, because they lead to both increased cardiac contractility and increased peripheral vasoconstriction eg Norepinephrine, Epinephrine and Dopamine

Norepinephrine- Inopressor

• Considered the safest Inopressor

• Less arrhythmogenic than Epinephrine and Dopamine

Mechanism of action

• Stimulates alpha-1 and alpha-2 receptors

• Small amount of beta-1 agonist- modest inotropic effect

• Increased coronary blood flow and afterload

• Increases venous tone and return with resultant increased preload

Adverse effects

• Norepinephrine is considered safer than both epinephrine and dopamine.

• Still carries risk of toxicity to cardiac myocytes, cardiac arrhythmias, and peripheral vasoconstriction leading to tissue ischemia

Indications

• Norepinephrine is considered first-line in cardiogenic shock with profound hypotension (SBP < 70 mm Hg)

• Should be used in conjunction with dobutamine in patients with cardiogenic shock and blood pressure higher than 70 mm Hg who fail to respond to dobutamine.

Dosing

• Use weight-based dosing to avoid the adverse effects associated with norepinephrine use

• Weight-based dosing is based on GFR

• Norepinephrine has a rapid onset of action (minutes) and can be titrated every 2-5 minutes

Dobutamine- Inopressor

Mechanism of action

• Stimulates beta-1 and beta-2 receptors at approximately a 3:1 ratio

• At high doses (greater than 15 ug/kg/min), dobutamine also becomes a mild alpha-1 agonist.

• Because it mainly stimulates beta-1 receptors, dobutamine is mostly an inotrope

• Dobutamine’s stimulation of beta-2 receptors can result in peripheral vasodilation, though the magnitude of this effect is variable à blood pressure in some (but not all) patients.

• Due to its vasodilatory effects, dobutamine has been shown to improve capillary perfusion independent of changes in blood pressure and cardiac index.

Adverse Effects

• Studies have demonstrated increased myocardial oxygen demand and malignant arrhythmias typically occuring at doses higher than 15 ug/kg/min

• Many patients experience hypotension associated with dobutamine use and should be used with caution in patients with systolic blood pressure less than 90 mmHg

• Dobutamine should only be used in patients with adequate fluid resuscitation

Indications

• Current ACC/AHA guidelines à first-line agent in management of hypotension associated with acute myocardial infarction

• But because dobutamine can lower BP, it should only be used if SBP is between 70-100 mmHg, with norepinephrine ready (or already infusing) as well.

• Dobutamine is typically recommended as the first line agent in cardiogenic shock , but this is not a strong recommendation because several studies have demonstrated benefits to norepinephrine in this setting.

• If dobutamine is used as a first-line agent, then norepinephrine should be second-line or already infusing, followed by milrinone.

Dosing

• Dobutamine can be started at 2 mcg/kg/min and titrated to effect, with a maximum dose of 20 mcg/kg/min.

• Onset of action is 1-2 minutes and the half-life is also approximately 2 minutes à rapidly reversible.

Milrinone- Inodilator

Mechanism of action

• Milrinone is a phosphodiesterase-3 (PDE3) inhibitor à leads to cardiac smooth muscle relaxation and peripheral vasoconstriction

• Potent inotropy + diastolic relaxation and vasodilation à to reduced preload, afterload, and systemic vascular resistance (SVR)

• Milrinone has no beta-adrenergic activity à minimal chronotropic effects.

Adverse Effects

• Because milrinone decreases preload (and therefore often leads to hypotension), it should only be used in patients who have undergone appropriate fluid resuscitation

• Use of milrinone often necessitates concurrent vasopressor administration.

• Because milrinone is metabolized in the kidneys, it should be avoided in patients with renal disease

Indications

• Recommended for use in patients with daily beta-blocker use and in patients with long-standing heart failure who have developed resistance to catecholamine derivatives

• Due to PDE’s vasodilatory effect on pulmonary vasculature à theoretical benefit in patients with pulmonary hypertension

Dosing

• The starting dose of milrinone should ideally be chosen based on that patient’s renal function. The general range is 0.25-0.75 mcg/kg/min.

• Avoid its use in patients with creatinine clearance less than 50 mL/min.

• Because of its long onset of action and half-life, milrinone should be titrated every 2 hours (or slower, in the presence of renal disease).

Vasopressin- Pressor

Mechanism of action

• Vasopressin is an endogenously released hormone (also known as anti-diuretic hormone) à vasopressin receptors in the kidneys à improve GFR

• Vasopressin receptors on the peripheral vasculature à vasoconstriction.

• Also causes coronary and cerebral vasodilation

Adverse Effects

• Vasopressin increases the risk of digital ischemia more significantly than the catecholamine derivatives.

• No evidence to support the use of vasopressin through a peripheral intravenous line

• Vasopressin does not have an antidote if extravasation does occur.

Indications

• Due to its increased risk for digital ischemia à avoid vasopressin in patients with known PVD

• It has been proposed that because vasopressin leads to coronary vasodilation, it may be a preferable agent in cardiogenic shock but few RCTs investigating vasopressin use in cardiogenic shock.

• Vasopressin may not lead to pulmonary vasoconstriction à ideal pressor choice in hypotension secondary to pulmonary hypertension à but not enough literature to support routine use in this setting

Dosing

Vasopressin is an endogenous à no utility to titrating vasopressin à used at a set dose of 0.04 U/min, regardless of weight.

Epinephrine- Inopressor

Mechanism of action

• Beta-1 and beta-2 receptors agonism à more inotropic effects than norepinephrine

• Epinephrine greatly increases chronotropy (heart rate) and thus stroke volume

• Some stimulatory effect on alpha-1 receptors

• Lower doses (1-10 mcg/min) à a beta-1 agonist

• Higher doses (greater than 10 mcg/min) à an alpha-1 agonist

Adverse effects

• Associated with an increased risk of tachycardia and lactic acidosis

• Hyperglycemia

• Increased incidence of arrhythmogenic events associated with epinephrine

• More difficult use lactate as a marker of the patient’s response to treatment

Indications

Should be used with extreme caution in cases of cardiogenic shock:

• RCT of 219 patients with cardiogenic shock found epinephrine to be independently associated with increased 90-day mortality and worsened renal function compared to dobutamine and norepinephrine (not validated).

• Known increased incidence of arrhythmogenic events associated with epinephrine

Dosing

• doses of 1-10 mcg/min predominantly activate beta-1 receptors, while doses greater than 10 mcg/min begin to primarily affect alpha-1-mediated vasoconstriction.

Phenylephrine: Not recommended in Cardiogenic shock

Resource: Awesome chart summarizing plessors

 http://www.emdocs.net/wp-content/uploads/2018/02/Inopressor-Summary_chart.pdf

References:

http://www.emdocs.net/evidence-based-approach-pressors-shock-part/

emDOCs.net – Emergency Medicine EducationAn Evidence-Based Approach to Pressors in Shock: Part I - emDOCs.net - Emergency Medicine Education

www.emdocs.net

http://www.emdocs.net/evidence-based-approach-pressors-shock-part-ii/

emDOCs.net – Emergency Medicine EducationAn Evidence-Based Approach to Pressors in Shock: Part II - emDOCs.net - Emergency Medicine Education

www.emdocs.net

Tarvasmäki T, Lassus J, Varpula M, Sionis A, Sund R, Køber L, et al. Current real-life use of vasopressors and inotropes in cardiogenic shock-adrenaline use is associated with excess organ injury and mortality. Critical Care. 2016;20(1):208.

Trauma in Pregnancy

Resuscitation of the Pregnant Trauma patient

General principles

·      Trauma is the most common cause of non-obstetrical maternal death in the United States

·      Best fetal resuscitation is good maternal resuscitation.

·      Stabilization of the pregnant women is the first priority; then, if the fetus is viable (≥ 23 weeks), fetal heart rate auscultation and fetal monitoring can be initiated and an obstetrical consultation obtained as soon as feasible

·      In Rh-negative pregnant trauma patients, quantification of maternal–fetal hemorrhage by tests such as Kleihauer-Betke should be done to determine the need for additional doses of anti-D immunoglobulin.

·      Tetanus vaccination is safe in pregnancy and should be given when indicated.

Airway

·      Greater risk for difficult intubation than non-pregnant patient

·      Pregnancy related changes à decreased functional residual capacity, reduced respiratory system compliance, increased airway resistance, and increased oxygen requirements

·      Gastric emptying is delayed in pregnancy à greater risk for aspiration

·      Respiratory tract mucosal edema à A smaller size of endotracheal tube is recommended

·      Choice of RSI medications NOT affected by pregnancy status

Breathing

·      Place chest tube one to 2 intercostal spaces higher than usual to account for displacement of the diaphragm during pregnancy

·      Marked increases in basal oxygen consumption à lower threshold for supplemental oxygen

Circulation

·      Fluid and Colloid resuscitation like standard trauma protocol

·      Uteroplacental vasculature is highly responsive to vasopressors, and their administration may decrease placental perfusion à vasopressors should be avoided unless refractory

·      Avoid supine hypotension: Compression of IVC by the uterus can cause up to 30% reduction in cardiac output à Place in left lateral position or by manual displacement of the uterus while the injured patient is secured in the supine position

·      O-negative blood should be transfused in order to avoid Rh sensitization in Rh-negative women

·      Vital signs: heart rate increases by 15% during pregnancy. Tachycardia and hypotension, typical of hypovolemic shock, may appear late in the pregnant trauma patient because of her increased blood volume.

·      Maternal vital signs and perfusion may be preserved at the expense of uteroplacental perfusion, delaying the occurrence of signs of hypovolemic shock

·      Attempt to obtain supra-diaphragmatic intravenous or intraosseous access for volume resuscitation and medication administration.

FAST

·      The FAST is less sensitive for free fluid in the pregnant patient than in non-pregnant patients.  Sensitivity decreases with increasing gestational age, likely due to altered fluid flow within the abdomen.

·      Management of suspected placental abruption should not be delayed pending confirmation by ultrasonography as ultrasound is not a sensitive tool for its diagnosis.

Secondary survey

·      In cases of vaginal bleeding at or after 23 weeks, speculum or digital vaginal examination should be deferred until placenta previa is excluded by a prior or current ultrasound scan.

Imaging

·      Radiographic studies indicated for maternal evaluation including abdominal computed tomography should not be deferred or delayed due to concerns regarding fetal exposure to radiation.

·      Ionizing radiation has the highest teratogenic potential during the period of organogenesis (5–10 weeks), with an increased risk of miscarriage before this period.

·      With abdominal CT during the third trimester the fetal exposure is around 3.5 rads, which is still under the threshold for fetal damage

·      Contrast agents should be used if indicated.

Resuscitative Hysterotomy in Cardiac Arrest

·      Should begin within 4 minutes and completed within 5 minutes of cardiac arrest

·      Both maternal and fetal survival decrease significantly after 5 minutes

·      Do NOT delay the procedure for the arrival of an obstetrician or neonatologist.

·      Do NOT evaluate for fetal cardiac activity or tocometry.

·      Do NOT prepare a sterile field (but be as clean as possible).

·      Do NOT transport to an alternative location.

·      Performing RH increases maternal cardiac output by 30%.

References:

Tamingthesru.com

EmDocs

Jain, Venu, et al. "Guidelines for the management of a pregnant trauma patient." Journal of Obstetrics and Gynaecology Canada 37.6 (2015): 553-571.

Smith, Kurt A., and Suzanne Bryce. "Trauma in the pregnant patient: an evidence-based approach to management." Emergency medicine practice 15.4 (2013): 1-18.