Grand Rounds Summary 10.10.18

The Great Debate - Epinephrine in Cardiac Arrest WITH DRS. MCMULLAN & HINCKLEY

Bolus Dose Epinephrine

Epinephrine is an alpha and beta-adrenergic medication, and its dosing matters in determining its primary effect. At low doses, the beta effect predominates leading to decreased systemic vascular resistance and decreased systemic perfusion. At high doses, e.g. 1 mg bolus, the alpha effects predominate and assist in increasing systemic vascular resistance. This may lead to increased chance of ROSC when given during cardiac arrest.

What is the optimal dose of epinephrine during cardiac arrest? This is not entirely known. A 2018 study in Resuscitation found that reducing the dose of epinephrine boluses given during cardiac arrest was not associated with any change in survival or any improvement in neurologic outcomes.1 A meta-analysis in 2000 evaluated standard dose epinephrine boluses versus higher doses (up to 15mg) and found no significant difference in hospital discharge rates, with a trend toward the standard doses being more favorable.2

Studies do show that early epinephrine administration is better. Every minute delay in initiating epinephrine decreases the chance of survival by 4%.3 Therefore, taking the time to create a drip can lead to detrimental delays in administration of epinephrine. And we know that standard dosing of epinephrine compared to giving no epinephrine does increase survival and increases ROSC.

Another argument against starting an adrenergic drip during cardiac arrest is that the drip is unlikely to work because of poor perfusion, poor circulation, and overall poor cardiac output. Additionally, it takes longer to set up and administer, you have no control over your dosing (particularly in the pre-hospital setting where providers have no pump and would likely have to rely on a “dirty epi-drip”), and it could lead to more drug errors (not all providers are comfortable setting this up). Finally, it may lead to an unnecessary diversion of resources in the pre-hospital or community setting where the primary focus should be on high-quality CPR, early defibrillation, and identification of the underlying cause of the arrest.

Continuous Epinephrine Drips

“The basic problem in resuscitation is securing a coronary perfusion pressure from 30-40 mmHG” (Crile and Dolley, 1906). Realistically, we probably need a minimum coronary perfusion pressure (CorPP) of 15 mmHg, but more is probably better. Recall that the CorPP is equal to the diastolic blood pressure (DBP) minus the central venous pressure (CVP).


What does this mean in cardiac arrest? In a 1990 study of 100 human cardiac arrest patients, the authors evaluated the CorPPs that were achieved during resuscitation. Their results showed that no one survived with CorPPs that were less than 15 mmHg. On the other hand, if the maximal CorPP achieved was greater than 25 mmHG, this correlated to a 79% survival rate.4 We know that epinephrine increases CorPP suggesting its benefit during cardiac arrest.

However, epinephrine is also known to decrease cerebral blood flow, is arrhythmogenic, and increases myocardial oxygen demand. Consequently, the goal is to balance the benefit that epinephrine can offer while minimizing its potential harms.

In the PARAMEDIC2 trial, no difference was seen in patients receiving standard dose epinephrine versus those who did not. In fact, patients who received epinephrine had worse modified Rankin scores.5 In the REASON trial evaluating the use of ultrasound in PEA arrest, the authors noticed that patient outcomes seemed to vary based on whether or not they received a continuous adrenergic drip (primarily norepinephrine and dopamine were used) during the arrest. 54% of patients receiving bolus epinephrine achieved ROSC versus 91% of patients receiving an adrenergic drip during the arrest. Similarly, 1.9% of patients receiving bolus epinephrine survived to hospital discharge versus 4.5% of patients receiving pressor drips. While this study was a small cohort and was not randomized, it seems to suggest that adrenergic support with a pressor drip may be beneficial during cardiac arrest.

Ultimately, initiating an adrenergic drip intra-arrest allows some cognitive offloading during the code, avoids the inevitable post-ROSC drop in blood pressure, and may lead to an improvement in outcomes.

Every other time we use pressors in resus, dosing is always guided by a goal-directed approach, and I see no reason we should just go with blind dosing in the most fragile of patients - the arrest patient - especially given the great potential for deleterious effects of too much epi in these folks
— Dr. Sam Ghali
  1. Fisk C, Olsufka M., Yin, L, McCoy A, et al. Lower-dose epinephrine administration and out-of hospital cardiac arrest outcomes. Resuscitation, 2018; 124:43-48.

  2. Vandycke C, Martens P. High dose versus standard dose epinephrine in cardiac arrest - a meta-analysis. Resuscitation, 2000; 45(3): 161-166.

  3. Hansen M, Schmicker R, Newgard C, Grunau B, et al. Time to epinephrine administration and survival from nonshockable out-of-hospital cardiac arrest among children and adults. Circulation, 2018; 137(19): 2032-2040.

  4. Paradis N, Martin G, Rivers E, Goetting M, et al. Coronary perfusion pressure and the return of spontaneous circulation in human cardiopulmonary resuscitation. JAMA, 1990; 263(8): 1106-1113.

  5. Perkins G, Chen J, Deakin C, Quinn, T, et al. A randomized trial of epinephrine in out-of-hospital cardiac arrest. NEJM, 2018; 379: 711-721.

R4 Case Follow-up: dialysis access  WITH DR. MURPHY

Dialysis Access

AV fistulas are an anastomosis between an artery and vein, typically performed in the upper extremity. Radiocephalic, brachiocephalic, and brachial artery to transposed basilic vein are the most common locations for fistula creation. The brachiocephalic fistula precludes future radiocephalic creation since it is more proximal, but it does have higher maturation success rates overall. Complications of fistulas include stenosis and thrombosis, bleeding, and infection. Nonetheless, when compared to grafts, fistulas have lower infection rates, greater long term patency rates, and less risk of steal syndrome. They are generally first line for most patients.  

A graft is a conduit between an artery and vein. These can be biologic (bovine) or synthetic (dacron/PFTE). The benefit of grafts is that they can connect vessels that are anatomically not amenable to fistulas. However, they have higher rates of thrombosis, infection, and steal syndrome.

Central venous catheters can also provide dialysis access. These can be tunneled or non-tunneled. The benefits of tunneled catheters include a lower infection risk, more comfort for the patient, and a lower risk of dislodgment. However, compared to fistulas and grafts there is a higher infection risk, so they are often only used for temporary dialysis.

Acute Limb Ischemia

Acute limb ischemia is defined as a time of two weeks or less. The symptoms are characterized by the “6 p's”: pain, pallor, paresthesias, pulselessness, poikilothermia, and paralysis. 85% are caused by a thrombus, most commonly due to underlying atherosclerosis. These patients typically have better collateral vessels and will have less impressive presentations. 15% of cases are caused by an embolus which is typically of cardiac origin. These patients are less likely to have collateral vessels and will therefore have an impressive clinical presentation, often manifesting with severe pain.  

The diagnosis is made by clinical suspicion followed by CT angiography. Relative blood pressures can be helpful when compared to a known baseline and the contralateral side. Ultrasound is less sensitive than CTA (80% vs >90%) but can also be performed. Cases are classified using the Rutherford Criteria.  Stage 1 is a viable limb that can be treated by urgent revascularization (12-36 hours). Stage 2 is characterized by sensory and motor findings and is a threatened limb. It requires emergent revascularization (<6 hours). Stage 3 occurs with loss of venous doppler signals and is an irreversibly damaged limb requiring primary amputation as the mainstay of treatment. In the ED, the management includes initiation of heparin or other anticoagulation and making arrangements for definitive therapy which is either endovascular or surgical revascularization. A recent review showed no difference in outcomes between these two methods.1 Of note, compartment syndrome can occur in 1 in 5 patients following revascularization, so close neurovascular monitoring is still required post-operatively.

  1. Enezate T, Omran J, Mahmud E, Patel M, et al. Endovascular versus surgical treatment for acute limb ischemia: a systematic review and meta-analysis of clinical trials. Cardiovascular Diagnosis and Therapy, 2017; 7(3): 264-271.

Pediatric Fractures WITH DR. Shah

It can be difficult to obtain good images in pediatrics. Consider starting with pain control in order to facilitate imaging of injured extremities.

Spiral Fractures (Toddler’s Fracture): Unique to children just starting to walk, and it can occur from a low mechanism injury. It is a spiral fracture of the tibial diaphysis. Treat with a splint and ortho follow-up. Even if not obvious on x-ray, consider splinting anyway and ensure appropriate follow-up.

Avascular Necrosis of Femoral Head (Legg-Calve-Perthes): This can be identified by a widened joint space with asymmetry of the hip, irregularity of femoral head, and there may be visible bone loss of the femoral head. It will require emergent orthopedic follow-up if the patient is unable to bear weight.

Slipped Capital Femoral Epiphysis: The femoral head falls off the neck (think ice cream falling off the cone). These require surgical fixation and emergent orthopedic follow-up if the patient is unable to bear weight

Forearm Buckle Fractures: Identified as an irregularity along the contour of the bone, but you may not actually see an obvious fracture. This should be splinted in a short arm volar splint. Follow-up in about one week with orthopedics.

Angulated Fractures of the Forearm: A general rule in the forearm is that if there is less than 15 degrees of angulation, you do not necessarily have to try to reduce the fracture. However, you should attempt reduction in fractures with more than 15 degrees of angulation.

Salter Harris Fractures: If any of these are displaced, these patients should be sent to a pediatric ED for reduction and close orthopedic follow-up.

  • I: Transverse fracture through physis: X-ray is often normal. Providers must have high index of suspicion based on point tenderness on exam. Treatment involves splinting and orthopedic follow-up.

  • II: Fracture extends into metaphysis: Should be splinted and given 1 week follow-up.

  • III: Fracture extends through epiphysis: Splint and provide 1 week follow-up.

  • IV: Fracture extends through epiphysis, physis, and metaphysis: Send to pediatric ED. These will need operative repair.

  • V: Compression of the physis: Send to a pediatric ED. These need emergent orthopedic evaluation.

Supracondylar Fractures: Evaluate for neurovascular compromise. If non-displaced, these may not require operative repair and can be placed in a posterior long-arm splint. Otherwise, most will require immediate orthopedic evaluation and likely operative fixation. Look for sail sign to identify occult fractures. This is present in the anterior fat pad due to hemarthrosis of the joint. The posterior fat pad sign, if present, is pathologic and suggests an occult fracture.