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To Push or Not to Push? Vasopressors Outside the Operating Room

14 Nov 2019 11:55 AM | MSHP Office (Administrator)

Authors: Caitlynn Tabaka, PharmD and

Livia Allen, PharmD, BCCCP

Learning Objectives

  1. Analyze the mechanism of action and pharmacokinetic properties of vasopressors to determine which vasopressor to use in specific scenarios.
  2. Identify the differences in dosing and preparation requirements for push-dose vasopressors.
  3. Evaluate current literature pertaining to the use of push-dose vasopressors outside of the operating room.
  4. Evaluate the safety concerns of utilizing push-dose vasopressors outside of the operating room.

Introduction

Vasopressors are excitatory and inhibitory agents utilized to increase a patient’s blood pressure through actions on the heart and/or vascular smooth muscle.1 They are traditionally administered through a central line as a continuous infusion for the management of fluid refractory systemic hypotension. Systemic hypotension is a medical emergency that can lead to end-organ ischemia if not managed properly.2 It is classified by a systolic blood pressure less than 90 mmHg, a diastolic blood pressure less than 60 mmHg or a mean arterial pressure less than 65 mmHg. The most common causes of hypotension include hypovolemic, cardiogenic, and distributive shock. Effective fluid resuscitation is crucial for stabilization of tissue hypoperfusion. The 2016 Surviving Sepsis Guidelines recommend that vasopressors be administered only once hypotension is found to be persistent despite adequate fluid challenges.3 

Vasopressor agents are typically administered as continuous infusions. However, bolus doses of vasopressors have been used to optimize a patient’s hemodynamic status when rapid intervention is required. This method of intermittently administering bolus vasopressor doses can be referred to as push-dose vasopressors, neo-sticks, or phenyl-sticks.4,5 Utilizing push-dose vasopressors to treat hypotension and maintain adequate perfusion is a common evidence-based practice by anesthesiologists in the operating room (OR). Studies that used push-dose epinephrine, phenylephrine, and ephedrine in the OR for hemodynamic management, secondary to sedation and spinal anesthesia, had positive outcomes. Push-dose vasopressors were shown to be as efficacious and safe as continuous infusion vasopressors and patients who received them required less vasopressors overall.6-9 Due to the success in the OR, the use of push-dose vasopressors has transitioned to the emergency department (ED) and intensive care unit (ICU) in recent years as a practical strategy to urgently manage hemodynamically unstable patients.

Hypotension in the ED and ICU settings are often multifactorial. Depending on the severity and duration, hypotension has been associated with acute organ failure, need for ICU stay, and in-hospital mortality. Potential etiologies include septic shock, post intubation hypotension, traumatic brain injury, transient hypotension related to procedural sedation, or while crystalloid or blood product volume resuscitation is in progress.4,5 In these cases, push-dose vasopressors may be given rapidly through a peripheral line to serve as a temporary bridging measure. Push-dose vasopressors can provide adequate perfusion to vital organs until a central line is placed and a continuous vasopressor infusion is initiated.4,10

Vasopressors

The most commonly used vasopressors for bolus dosing are epinephrine and phenylephrine.4,5 Phenylephrine is preferred over epinephrine in patients who present with tachycardia or tachyarrhythmias.Similarly, push-dose norepinephrine has recently gained attention in the anesthesia literature due to its lower tendency to cause tachycardia. Norepinephrine also has the quickest onset and shortest duration of action. It can be utilized in a setting where quick on and offset of a vasopressor is desirable. Evidence supporting the use of push-dose norepinephrine outside the OR is lacking.11-14 Ephedrine is popular among the anesthesiologists due to its extended duration of action, however, using a product with an extended duration in the ED or ICU could lead to overcorrection of hypotension and bradycardia.4,16


Literature

The available literature consists of efficacy and safety evaluations of push-dose vasopressors for the management of hypotension. The evidence is currently limited to case series and retrospective studies conducted in the ED and ICU settings. Results from prospective, randomized controlled trials are not yet available. The two main push-dose vasopressors analyzed were epinephrine and phenylephrine with only one study evaluating the use of ephedrine and none evaluating norepinephrine. 10, 17-20 Push-dose vasopressors were used for a variety of indications including sepsis, respiratory distress/failure, cardiac arrest, trauma-induced hypotension, and post-intubation or procedural sedation induced hypotension.10, 17-20

 There was a wide range of doses and dosing frequencies between the studies. Only one study had a protocol in place with standard dosing regimens of push-dose vasopressors.20 Most of the patients included in the studies were transitioned to continuous infusion vasopressors. The three patient cases described by Gottlieb et al. required continuous norepinephrine to maintain hemodynamic control after receiving push-dose epinephrine.19 Schwartz et al. evaluated the need for continuous support within 30 minutes following push-dose vasopressors.18 They found that patients who were appropriately fluid challenged required less vasopressor boluses and had a lower rate of continuous vasopressor infusions compared to those inadequately fluid challenged. Only two other studies assessed patients that received adequate fluid resuscitation prior to the initiation of push-dose vasopressors.19,20 The most common adverse effects noted in the literature include bradycardia, hypertension, and tachycardia. Rotando et al. reported that 11% of the included patients had a dose related medication error.20 Overall, the studies concluded that further assessments of appropriateness, efficacy, and safety need to be conducted for the use of push-dose vasopressors outside of the OR.10,17-20


Push-Dose Vasopressor Preparation

Push-dose vasopressor concentrations are not available commercially and must be prepared at bedside prior to administration. The preparation generally involves diluting commercially available products with normal saline (NS) to achieve appropriate concentrations. It is recommended that organizations preparing and utilizing these products develop a standardized process for naming, dosing, ordering, preparing and administering push-dose vasopressors.4


Safety Concerns

Vasopressors are strong vasoconstrictors that can lead to tissue hypoperfusion and injury if extravasation occurs. The risk of extravasation is greater when administered peripherally versus centrally. Studies have shown the vast majority of vasopressor-induced tissue damage occurs in peripheral lines that are distal to the antecubital or popliteal fossa and when infused for greater than four hours.21 Peripheral administration of vasopressors should be monitored frequently and reserved for emergency situations as a temporizing measure until central venous access can be obtained. If dosed correctly, push-dose vasopressors can be a great way to prevent peripheral extravasation due to the administration of small intermittent doses at diluted concentrations. Additional adverse effects that can occur when push-dose vasopressors are dosed incorrectly include local skin and soft-tissue injury (necrosis), end-organ tissue ischemia, acute hypertension, cardiac ischemic events, and left ventricular dysfunction.22

Ensuring patient safety in the ED setting can be challenging due to treatment of unfamiliar patients, crowding, high stress situation, reliance on verbal orders, and dispensing and administering medications without verification by a pharmacist.4 The risk of error increases when utilizing push-dose vasopressors because of required dose calculations, drug dilutions, and incremental push-dose administrations. Errors in preparation, drug selection, and administration have been frequently reported. Acquisto et al.describes patients receiving high doses of push-dose epinephrine and phenylephrine due to dosing errors.23 In one case, a post-surgical hypovolemic shock patient developed hypotension during transport. Once in the ICU, the physician ordered “phenylephrine 50” and the patient was given 50 mg instead of the intended 50 mcg push dose. Another case occurred when a post-surgical patient developed atrial fibrillation and was treated with diltiazem IV boluses. The patient developed asymptomatic hypotension and a phenylephrine push-dose was ordered. In this case, the entire 1000 mcg phenylephrine pre-mixed syringe was administered instead of the intended 100 mcg. In both cases, fluid resuscitation had not been implemented prior to the initiation of push-dose vasopressors.

Another common push-dose vasopressor error includes physicians asking for epinephrine mixed to the 100 mcg/mL phenylephrine concentration instead of the 5-20 mcg/mL epinephrine concentration. Epinephrine is available in various doses and concentrations to be delivered by multiple routes depending on the indication. Four cases related to dosing errors of push-dose epinephrine resulted in cardiogenic shock, ST-elevation myocardial infarction, and ventricular tachycardia.22 Contribution to these errors were multifactorial and included inadequate physician knowledge about appropriate dose and route of epinephrine, complicated dose calculations involving decimals and ratios, and lack of adequate communication between physicians and nurses. The Institute for Safe Medication Practices (ISMP) has Safe Practice Guidelines for Adult IV Push Medications that states a lack of administrative policies/protocols/guidelines for IV injections is a risk factor for error.24 ISMP recommends guidelines for parenteral medications through IV push administration route should be simplified, standardized, and communicate safe practices associated with the IV medication.

Conclusion

Successful practice migration from the operating room to the ED and ICU has been a continuous process for ages. The use of succinylcholine and other neuromuscular blockers for rapid sequence intubation was reserved for the OR until rigorous clinical research evaluating the utilization of neuromuscular blockers for procedures in the ED demonstrated superior outcomes.25,26 Propofol for procedural sedation has a similar history. It was only being utilized in the OR until clinical trials demonstrated that it was safe and effective for procedural sedation in the ED and ICU settings.27,28 Both of these practices that were initially met with resistance are now mainstay practices in the ED and ICU.

The resistance against the migration of push-dose vasopressors to the ED and ICU stems from the limited literature available evaluating efficacy and safety. The studies available are retrospective and have several notable limitations including significant variations in dosing and timing of administration, reduced utilization of crystalloid fluids, and small patient sample sizes. Overall there is a lack of clear systematic practice patterns concerning the use of vasopressors which lead to adverse effects and medical errors. Currently, there are no guidelines discussing the management of an unintentional push-dose vasopressor overdose. Tachycardia, hypertension, and reflexive bradycardia are the most likely adverse effects of these agents when utilizing bolus dosing. Due to the short half-lives of these agents the adverse effects should not last longer than 30 minutes. However, in extreme overdoses more severe adverse events may occur including arrhythmias, limb ischemia, hypertension leading cerebrovascular events, metabolic acidemia, and lactic acidosis.1,4

Institutions that implement push-dose vasopressors should have clear protocols and procedures indicating appropriate patients, medications, doses, preparation, and administration for push-dose vasopressors. If used at all, push-dose vasopressors should only be utilized as a temporary bridging measure until a continuous vasopressor infusion can be initiated. Push-dose vasopressors should only be used in those patients who have received adequate fluid resuscitation.18,19 Further studies need to be conducted to evaluate the safety and efficacy of utilizing push-dose vasopressors outside of the OR.

References

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  2. Kellum J, Pinsky M. Use of Vasopressor Agents in Critically Ill Patients. Curr Opin Crit Care. 2002 June;8(3):236-41.
  3. Rhodes A, Evans L, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-377.
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  6. Siddik-Sayyid S, Taha S, Kanazi G, et al. A randomized controlled trial of variable rate phenylephrine infusion with rescue phenylephrine boluses versus rescue boluses alone on physician interventions during spinal anesthesia for elective cesarean delivery. Anesth Analg. 2014; 118:611-618.
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  12. Wang X, Shen X, Liu S, et al. The Efficacy and Safety of Norepinephrine and Its Feasibility as a Replacement for Phenylephrine to Manage Maternal Hypotension during Elective Cesarean Delivery under Spinal Anesthesia. Biomed Res Int. 2018; 2018:1869189.
  13. Hassani V, Movaseghi G, Safaeeyan R, et al. Comparison of Ephedrine vs. Norepinephrine in Treating Anesthesia-Induced Hypotension in Hypertensive Patients: Randomized Double-Blinded Study. Anesth Pain Med. 2018;8(4):e79626.
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  18. Schwartz M, Ferreira J, Aaronson P. The impact of push-dose phenylephrine use on subsequent preload expansion in the ED setting. American Journal of Emergency Medicine. 2016; 34:2419-2422.
  19. Gottlieb M. Bolus dose of epinephrine for refractory post-arrest hypotension. CJEM. 2018; 20(S2):S9-13.
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