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


  • 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.


  • 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


  • 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.


  • 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


  • 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


  • 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.


  • 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


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



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



  • 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


References: – Emergency Medicine EducationAn Evidence-Based Approach to Pressors in Shock: Part I - - Emergency Medicine Education – Emergency Medicine EducationAn Evidence-Based Approach to Pressors in Shock: Part II - - Emergency Medicine Education


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.




·      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



·      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



·      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.




·      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.



·      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%.


RH Algorithm.png




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.



Resuscitative TEE

Important: Please complete the Sexual Harassment Online Module ASAP!

Resuscitative Transesophageal echocardiography (TEE)

  • TEE allows the emergency physician to maintain the standard of an ultrasound-informed resuscitation in the scenario of cardiac arrest, where TTE is significantly limited.

  • Focused or resuscitative TEE (4 views) differ from comprehensive TEE (>20 views) that cardiology performs in that it is employed to identify specific questions.

  • TEE allows for potentially shorter chest compression pauses

  • TEE allows for evaluation for the quality of chest compressions

  • TEE allows for visualization of fine V-fib not seen on the monitor


Indications: Cardiac arrest (ACEP)

Contraindications: Esophageal injury or stricture and lack of a definitive airway

How to manipulate a TEE Probe:

5 different ways you can physically manipulate the TEE probe

1. Withdraw or Advance up or down patient’s esophagus

2. Turn probe to right or left

3. Turn tip of flip in anterior- ante-flexing or in the posterior direction called retro-flexing --> large wheel

4. Turn tip to Left or right -->  small wheel (not typically used for our purposes)

5. In addition, you can rotate the transducer housed within the probe itself (AKA omniplane or multiplane)-->  adjusts the beam angle anywhere between 0° and 180° -->  two smaller buttons ( crystal rotation)

TEE manipulation.jpg


TEE-controls- wheels.png



The views are obtained in the following order: : 

The midesophageal 4-chamber view (ME 4C) is obtained by advancing the TEE probe to the thoracic esophagus and orienting the multiplane at 0-20° in neutral flexion. You may need to retroflex slightly to see all four chambers.

-   The midesophageal long-axis view (ME LAX) is obtained by leaving the probe in the same location as the midesophageal 4-chamber, but increasing the multiplane to between 110° and 160° while in neutral flexion. 

-   The transgastric short axis view (TG- SAX) is obtained by first moving the multiplane to 0°, then advancing the probe into the stomach and ante-flexing the probe

-   The bicaval view (ME bicaval) is obtained by turning the entire probe to the patient’s right towards the superior vena cava (SVC) and inferior vena cava (IVC) while in the mid-esophagus, keeping the multiplane at 90-100° with neutral flexion

 ( The first 3 views are recommended by ACEP. Bicaval not recommended by ACEP) 

TEE views and their analogous TTE views


Midesophageal four chamber view (ME 4C)

-  Apical four chamber view

-  Great visualization of all chambers as well as the tricuspid and mitral valves in one plane.

-   Evaluation of right and left ventricular systolic function and size

-   Preferred view to evaluate for the presence or absence of a perfusing rhythm during a pulse check.



Midesophageal Aortic Long Axis view (ME LAX)

-  Midesophageal analogous to the parasternal long axis view in TTE

-   View includes the mitral and aortic valves, as well as the left atrium, left ventricle, and left ventricular outflow tract of the right ventricle.

-   Evaluate left ventricular systolic function, and provides feedback on compression adequacy and location. High-quality compressions cause maximal compression of the left ventricle and visualization of the aortic valve opening and closing indicating forward flow of blood.  Poor quality compressions are seen over the aortic root and there is no valvular indication of forward flow. 

ME- LAX.png


Transgastric Short Axis view (TG- SAX)

- Analogous to the parasternal short axis TTE view

- Evaluate left ventricular systolic function, including any regional wall motion abnormalities

- Can evaluate for acute MI and the presence of septal flattening in this view


Mid Esophageal Bicaval View (ME bicaval)

-   Analogous to the inferior vena cava view of TTE

-   Transducer plane cuts through the left atrium (LA), right atrium (RA), IVC and SVC.

This view allows the operator to evaluate for hypovolemia, atrial size, and interatrial septum bowing.

-   Aids in the placement of central venous catheters, transvenous pacemakers, or extracorporeal life support (ECMO) vascular cannulas by observing the initial wire placement in the vasculature

- Can aid inevaluation of fluid status to guide fluid resuscitation (looking at respiratory variation in SVC)




-  Compressions do not need to be stopped for TEE insertion. Additionally, the TEE can be left in the esophagus during defibrillation. The probe should be inserted or withdrawn while the tip is in neutral position, and not while the tip is flexed to avoid esophageal injury. 

-  Images should be optimized to avoid foreshortening of the ventricles and to include the appropriate structures for each view.

-  Pericardial effusions must be taken into clinical context, as small effusions can cause tamponade if accumulated rapidly, while large effusions can be well tolerated if they accumulate slowly.

-   Clotted hemopericardium may be isoechoic with the myocardium, making it difficult to identify.

-  Right ventricular failure is not specific to pulmonary embolism, and can be due to pulmonary hypertension or other etiologies such as right sided myocardial infarction, or even cardiac arrest itself.

-  Pleural effusions can be mistaken for pericardial effusions. Multiple views should be used to corroborate findings.

-  Fat pads can be mistaken for pericardial effusions, but these are hypoechoic rather than anechoic and limited to the anterior and apical regions of the heart, not circumferential.



Check out this 3D module that you can practice on


Drs Lawrence Haines, Judy Lin and Alyssa Phuoc-Ngyuyen

Images: Adapted from Arntfield R, Pace J, McLeod S, et al. Focused transesophageal echocardiography for emergency physicians-description and results from simulation training of a structured four-view examination. Crit Ultrasound J. 2015;7(1):27.

Teran, Felipe, et al. "Evaluation of out-of-hospital cardiac arrest using transesophageal echocardiography in the emergency department." Resuscitation 137 (2019): 140-147.


ACEP policy statement


Indications for use of Tranexamic Acid (TXA)

Indications for use of Tranexamic Acid (TXA)



Trial Name: CRASH 2 (Positive trial)

Trial Type: Multicenter, double-blind RCT

Sample size: 20,211

Dose/Route of TXA: Loading dose 1g over 10 min, then infusion of 1g over 8hr

Primary outcome: All-cause mortality within 4 weeks of injury

Secondary outcome: Vascular occlusive events (AMI, stroke, PE, and DVT), surgical intervention, receipt of blood transfusion, and units of blood products transfused

Results:  Reduced All-cause mortality p 0.0035, death due to hemorrhage p 0.0077, no significant vascular occlusion p 0.96

Risk of thrombotic events: No increase in risk

Take home point: The use of TXA in trauma patients with “significant bleeding” reduces all-cause mortality without an increase in thromboembolic events.  This effect seems to be greatest in the subset of patients with severe shock (SBP ≤70mmHg) and when given ≤3 hours from time of injury 


Shakur H et al. Effects of Tranexamic Acid on Death, Vascular Occlusive Events, and Blood Transfusion in Trauma Patients with Significant Haemorrhage. Lancet 2010. PMID: 20554319


Trial Name: MATTERs (Positive trial)

Trial Type: Single center, retrospective, observational study

Sample size: 896

Dose/ route of TXA: 1 g initially, 2nd dose per MD discretion

Primary outcome: 24hr mortality, 48hr mortality, and 30-day mortality

Secondary outcome: Transfusion requirements and rate of thromboembolic complications.

Results: Not significantly decreased 24 hr p >0.05, Significantly decreased 48hrs p 0.004 and 30 day mortality p 0.03

Risk of thrombotic events: Increased overall VTE p 0.001 but patients who had a VTE also had higher burden of injury

Take home point:  Patients with penetrating injuries, requiring blood transfusions within 1hr of presentation the use of TXA reduced overall mortality


Morrison JJ et al. Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study. Arch Surg 2012. PMID: 22006852





Trial Name: Meta-Analysis of TXA for Traumatic Brain Injury- negative trial

Trial Type: Meta-analysis and systematic review of RCTs or quasi-RCTs 

Sample size:  510

Outcome: Mortality, neurological function, hematoma expansion

Results: statistically significant reduction in ICH progression with TXA non-statistically significant improvement of clinical outcomes in ED patients with TBI.

Risk of thrombotic events: No adverse effects reported

Take home point: Did not lead to a statistically significant mortality benefit or improved neurological functional status. Further evidence is required to support its routine use in patients with TBI.


Zehtabchi S et al. Tranexamic Acid for Traumatic Brain Injury: A Systematic Review and Meta-Analysis. Am J Emerg Med 2014. PMID: 25447601



Trial Name: Tranexamic Acid for Hyperacute Primary IntraCerebral Haemorrhage (TICH-2)- Negative

Trial Type: International, randomized, double-blind, placebo-controlled, parallel group

Sample size:  2325

Dose of TXA used: 1g IV TXA bolus followed by an 8hr infusion of 1g of TXA 

Outcome:  Functional Status at Day 90, Hematoma Expansion at Day 2, Mean Hematoma Volume Expansion from Baseline to 24hr, Death by Day 7, Death by Day 90

Results: No difference in neurological impairment (mean NIHSS score at day 7), 90-day functional outcomes, length of hospital stay, discharge disposition, venous thromboembolic events, or arterial occlusions

Risk of thrombotic events: None

Take home point: TXA was given >3hrs after stroke onset, patients had more severe strokes, and larger hematoma volumes (>60mLs) than prior studies. Possible benefit if given to a subset of patient within 3 hours with smaller strokes but cannot be recommended at this time in clinical practice for spontaneous ICH based on the results of these trials


Sprigg N et al. Tranexamic Acid for Hyperacute Primary IntraCerebral Haemorrhage (TICH-2): An International Randomised, Placebo-Controlled, Phase 3 Superiority Trial. Lancet 2018. PMID: 29778325



Post Partum Hemorrhage


Trial Name: WOMAN trial – Negative trial

Trial Type: Randomized, double-blind, placebo-controlled trial,

Sample size:  20,060 ≥16 years of age with post-partum hemorrhage after vaginal delivery or caesarean section 

Dose of TXA used: 1 g IV vs matching placebo, If bleeding continued after 30 minutes or stopped and restarted within 24hrs, a second dose of 1g of TXA or placebo was given

Outcome: Initial outcome of all-cause mortality and/or hysterectomy within 42 days of giving birth

Final Primary Outcome: Death from PPH

Results: No difference in all cause mortality or hysterctomy

Risk of thrombotic events:

Take home point: It is difficult to draw definitive conclusions from this trial as the NNT was still large (i.e. ≈250) and the study had a fragility index of 0. Data showed a consistent association of delayed administration of TXA with no benefit

WOMAN Trial Collaborators. Effect of Early Tranexamic Acid Administration on Mortality, Hysterectomy, and Other Morbidities in Women with Post-Partum Haemorrhage (WOMAN): An International, Randomised, Double-Blind, Placebo-Controlled Trial. Lancet 2017. PMID: 28456509




Trial Name: Cochrane review

Trial Type: Systematic review and meta-analysis of 8 RCTs

Sample size:  1700

Dose of TXA used: Total daily dose of TXA ranged from 4 – 8g and ranged from 2 – 7 days with both PO and IV adminsteration

Outcome: Primary: all-cause mortality and adverse events

Secondary: Rebleeding and surgery

Results: All-Cause Mortality p 0.007, rebleeding P = 0.07

Risk of thrombotic events: No difference in thromboembolic events (only evaluated in 4 trials)

Take home point: May benefit in higher risk patients but better RCTs required to confirm or refute evidence. HALT IT trial underway currently with N of 12000


Bennett C et al. Tranexamic Acid for Upper Gastrointestinal Bleeding (Review). Cochrane Database Syst Rev 2014. PMID: 25414987





Trial Name: Zahed et al 2017 – Positive study

Trial Type: Randomized, parallel group clinical trial

Sample size:  124 on antiplatelets

Dose of TXA used: topical TXA (500mg in 5mL) or anterior nasal packing.

Outcome: Primary outcome resolution at 10 minutes. Secondary outcomes were re-bleeding rate at 24hours and one week, ED length of stay, and patient satisfaction

Results: epistaxis treatment with topical application of TXA resulted in faster bleeding cessation (NNT 2) , less re-bleeding at 1-week, shorter ED LOS, and higher patient satisfaction as compared with anterior nasal packing.

Risk of thrombotic events: not evaluated

Take home point: Do it!

Zahed R et al. Topical Tranexamic Acid Compared With Anterior Nasal Packing or Treatment of Epistaxis in Patients Taking Antiplatelet Drugs: Randomized Controlled Trial. Acad Emerg Med 2017. PMID: 29125679


Post-Tonsillectomy Bleeding


Trial Name: Meta-Analysis 2012

Trial Type: Systematic review and meta-analysis

Sample size:  7 studies with 2,444 patients

Dose of TXA used: 250mg for children <25kg, 500mg for children >25kg

Outcome: mean volume of blood loss

Results: TXA led to a significant reduction of tonsillectomy blood loss volume but had no impact on the rate of patients with post-tonsillectomy hemorrhage.

Risk of thrombotic events: Not evaluated

Take home point:  In patients with minor post-tonsillectomy bleeding consider using nebulized TXA to reduce or stop bleeding.  

Chan CC et al. Systematic Review and Meta-Analysis of the Use of Tranexamic Acid in Tonsillectomy. Eur Arch Otorhinolaryngol 2013. PMID: 22996082


Heavy Menstrual Bleeding


Trial Name: Cochrane Review

Trial Type: Systematic review and metanalysis

Sample size:  1312 in 13 RCTs

Dose of TXA used: majority of studies used regular dose TXA (ranging from 3 g/day to 4 g/day), Four other studies used low‐dose TXA (ranging from 2 g/day to 2.4 g/day) 

Outcome: Volume of blood loss, Quality of life

Results:  Appears effective for treating HMB compared to placebo, NSAIDs, Oral luteal progestogens, ethamsylate or herbal remedies but less effective than levonorgestrel intrauterine system

Risk of thrombotic events: Not studied in most RCTs

Take Home point: Antifibrinolytic treatment (such as TXA) appears effective for treating HMB compared to placebo, NSAIDs, oral luteal progestogens, ethamsylate, or herbal remedies. There were too few data for most comparisons to determine whether antifibrinolytics were associated with increased risk of adverse events, and most studies did not specifically include thromboembolism as an outcome.


Bryant-Smith AC, Lethaby A, Farquhar C, Hickey M. Antifibrinolytics for heavy menstrual bleeding. Cochrane Database of Systematic Reviews 2018, Issue 4. Art. No.: CD000249. DOI: 10.1002/14651858.CD000249.pub2



Trial Name: Inhaled TXA RCT 2018

Trial Type: Prospective, double-blind, placebo-controlled randomized controlled trial 

Sample size:  47

Dose of TXA used: nebulized TXA (500mg/5mL

Primary outcome: rate of complete resolution of hemoptysis during first 5 days from admission, difference in daily volume of expectorated blood

Secondary outcome: rate of interventional bronchoscopy, rate of angiographic embolization, rate of surgery, mean hospital LOS

Results: Resolution of hemoptysis within 5 days of admission, NNT = 2, P<0.0005. Statistically shorter LOS, less invasive procedures

Risk of thrombotic events: not studied

Take home point: Although this was a small study, the advantages of inhaled TXA vs placebo in patients with non-massive hemoptysis included faster resolution of hemoptysis, shorter hospital LOS, fewer invasive procedures, and although not statistically significant, a trend toward improved 30d mortality.


Wand O et al. Inhaled Tranexamic Acid for Hemoptysis Treatment: A Randomized Controlled Trial. Chest 2018. PMID: 30321510



See above




“Pressors” in Distributive Shock in Adults

“Pressors” in Distributive Shock in Adults

Thank you, Dr Dastmalchi, for requesting this POTD. I will review “pressors” for cardiogenic shock separately

  • 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

  • First line vasopressor in septic shock per Surviving Sepsis Guidelines

  • 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.

  • ARR of 11% compared to dopamine with NNT 9

  • NE superior in improving CVP, urinary output, and arterial lactate levels compared to Epinephrine, Phenylephrine, and Vasopressin.


  • First-line pressor choice in distributive shock, including both neurogenic and septic shock

  • Norepinephrine as the only first-line pressor per SSC guidelines


  • 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

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


  • SSC guidelines recommend epinephrine as a second-line agent, after norepinephrine

  • “push-dose pressor”

  • Due to beta-2 receptors agonism causing bronchodilation, epinephrine is first-line agent for anaphylactic shock


  • Guidelines for anaphylactic shock recommend an initial bolus of 0.1 mg (1:10,000) over 5 minutes, followed by an infusion of 2-15 mcg/min however associated with adverse cardiovascular events

  • For septic shock start epinephrine at 0.05 mcg/kg/min (generally 3-5 mcg/min) and titrate by 0.05 to 0.2 mcg/kg/min every 10 minutes. maximum drip rate is 2 mcg/kg/min

Dopamine- Inopressor

  • Fallen out of favor

  • Associated with higher arrhythmogenic events

Mechanism of action

  • Effects are dose-dependent

  • Low doses à dopaminergic receptors à leads to renal vasodilation à increased renal blood flow and GFR although studies failed to demonstrate improved renal function with dopamine use clinically

  • Moderate doses à beta-1 agonism à increased cardiac contractility and heart rate

  • High doses à alpha-1 adrenergic effects à arterial vasoconstriction and increased blood pressure

Adverse Effects

  • Several large, multi-center studies that demonstrate increased morbidity associated with its use

  • Significantly higher rates of dysrhythmias à NNH 9


  • Rescue medication when shock is refractory to other medications


  • Start at 2 mcg/kg/min and titrate to a maximum dose of 20 mcg/kg/min.

  • Less than < 5 mcg/kg/min à vasodilation in the renal vasculature

  • 5-10mcg/kg/min à beta-1 agonism

  • 10 mcg/kg/min à alpha-1 adrenergic

Vasopressin- Vasopressor

  • Add vasopressin (doses up to 0.04 units/min) to norepinephrine to help achieve MAP target or decrease norepinephrine dosage

  • Restore catecholamine receptor responsiveness, particularly in cases of severe metabolic acidosis.

  • pH independent

  • Pure pressor à increase vasoconstriction with minimal effects on chronotropy or ionotropy

Mechanism of action

  • At low doses (< 0.04 units/min) à increases vascular resistance (V1)

  • No effect on heart rate and cardiac contractility

Adverse Effects

  • Vasopressin has been shown to be as safe as norepinephrine at lower doses

  • Increases SVR and afterload and decreases cardiac output although unclear if effect significant at lower doses


  • Second line vasopressors per SSC guidelines for septic shock

  • pH independent- Vasopressin in combination with epinephrine demonstrated improved ROSC in cardiac arrest patients with initial arterial pH <7.2 compared with epinephrine alone


  • Steady dose at 0.03-0.04 units/min

  • Vasopressin is not titrated to clinical effect as are other vasopressors

  • Think about it more as a replacement therapy and treatment of relative vasopressin deficiency

Phenylephrine- Vasopressor

  • Pure pressor à increase vasoconstriction with minimal effects on chronotropy or ionotropy

  • SSC guidelines does not make rated recommendations on Phenylephrine

  • Limited clinical trial data

Mechanism of action

α1 agonism with peripheral vasoconstriction

Adverse Effects

  • Bradycardia - decrease in heart rate mediated by the carotid baroreceptor reflex 2/2 increase in SVR

  • Increases SVR and afterload and decreases cardiac output


  • Patients that are susceptible to beta-adrenergic generated arrhythmia

  • Push dose formulation

  • Refractory shock


0.1-2mcg/kg/min (onset: minutes, duration: up to ~20 minutes)




Pollard, Sacha, Stephanie B. Edwin, and Cesar Alaniz. "Vasopressor and inotropic management of patients with septic shock." Pharmacy and Therapeutics 40.7 (2015): 438.

Amlal, Hassane, Sulaiman Sheriff, and Manoocher Soleimani. "Upregulation of collecting duct aquaporin-2 by metabolic acidosis: role of vasopressin." American Journal of Physiology-Cell Physiology 286.5 (2004): C1019-C1030.

Khanna, Ashish, and Nicholas A. Peters. "The Vasopressor Toolbox for Defending Blood Pressure."

Turner, DeAnna W., Rebecca L. Attridge, and Darrel W. Hughes. "Vasopressin associated with an increase in return of spontaneous circulation in acidotic cardiopulmonary arrest patients." Annals of Pharmacotherapy 48.8 (2014): 986-991.


Targeted Temperature Management

Great job on resuscitating that V fib cardiac arrest and achieving sustained ROSC. 

Now what? Cool them!

Whether you cool them or not could determine whether your patient goes into multisystem organ failure in the ICU or walks out of the hospital few weeks later.



Targeted temperature management (TTM) to improve survival and neurological outcomes among comatose survivors of patients with cardiac arrest



Adults with out-of-hospital cardiac arrest with an initial shockable rhythm and nonshockable rhythm


Inclusion criteria (must meet all criteria)

  • Postcardiac arrest status (any rhythm as a cause of arrest is eligible)

  • ROSC < 30 minutes from EMS/code team arrival

  • Time at induction < 6 hours from ROSC

  • Comatose status (patient does not follow commands)

  • MAP ≥ 65 mm Hg (may include use of vasopressor drugs)

Exclusions may include

  • DNR advanced directive, MOLST, poor baseline status, or terminal disease

  • Traumatic etiology for the arrest

  • Active bleeding or known intracranial bleeding (relative)

  • Cryoglobulinemia (relative)

  • Pregnancy (relative; consider obstetrician/gynecologist consultation)

  • Recent major surgical procedure (relative)

  • Severe sepsis/septic shock as cause of arrest (relative)


  • Decreased fever-related tissue injury

  • Reduction in ischemic-reperfusion injury

  • Cerebral metabolic rate decreases by a 6-7% for every 1ºC drop in body temperature which reducing oxygen demand, preserving phosphate compounds and preventing lactate production and acidosis

  • Bernard, et al (2002) found an Absolute Risk Reduction (ARR) for death or severe disability of 23%, NNT was 4.5

  • The Hypothermia After Cardiac Arrest (HACA) Group (2002) found an ARR for unfavourable neurological outcome of 24%, and NNT of 4


  • IV cold saline 2-3 mL/kg

  • Cooling vest and cooling machine- Arctic Sun

  • If shivering does not occur, do not use neuromuscular blockade

  • If paralysis employed, titrate to degree of shivering- do not need train-of-four monitoring

  • Sedation of choice is institution dependent (MMC CICU uses Fentanyl and Midazolam)


Initiation of TTM within122 minutesof hospital admission was associated with improved survival.
Most guidelines recommend initiation within6 hours

What temperature should be targeted:

This remains controversial, with guidelines accepting a range of temperature targets from 33-36C. Available evidence shows no benefit to hypothermia (33C) compared to normothermia (36C). In the absence of evidence, targeting 36C is prudent

  • TTM36 is more hemodynamically stable than TTM33, which is relevant because these are often very unstable patients.

  • TTM36 avoids electrolytic shifts associated with raising and lowering the temperature.

  • Hypothermia at 33C suppresses immune function and associates with increased rates of pneumonia.

  • TM33 will induce bradycardia, which is dangerous in patients with underlying torsades de pointes.


Bernard SA et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 2002;346:557-63. PMID 11856794

Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 2002;346:549-56. PMID 11856793

Nielsen N et al. Targeted temperature management at 33 degrees C versus 36 degrees C after cardiac arrest. N Engl J Med 2013; 369: 2197-206. PMID 24237006

Stanger, Dylan, et al. "Door‐to‐targeted temperature management initiation time and outcomes in out‐of‐hospital cardiac arrest: insights from the Continuous Chest Compressions Trial." Journal of the American Heart Association 8.9 (2019): e012001.

Donnino, Michael W., et al. "Temperature management after cardiac arrest: an advisory statement by the advanced life support task force of the international liaison committee on resuscitation and the American Heart Association emergency cardiovascular care committee and the council on cardiopulmonary, critical care, Perioperative and Resuscitation." Circulation 132.25 (2015): 2448-2456.

EB Medicine
Mayo Clinic Florida TTM Guideline