Are push-dose vasopressors (PDPs) safe and effective for patients with hypotension outside the operating room? This Concise Critical Appraisal covers a recent study that sought to determine whether phenylephrine and epinephrine are effective for acute hypotensive periods when PDP protocols are in place.
Hypotension can lead to significant organ dysfunction, including lowering coronary artery perfusion pressure leading to myocardial ischemia and an increased risk of cardiac arrest. The ill effects of hypotension are a result of not only severity but also duration of the hypoperfused state. To promptly treat hypotension, push-dose vasopressors (PDPs) are used at many institutions to overcome the inherent delay in vasopressor infusion administration.
1 Vasopressor choice may depend on the availability of a premixed drug and the side effect profile in a specific scenario.
Singer et al recently aimed to identify the practice patterns and safety and efficacy of the more commonly used PDPs, phenylephrine and epinephrine, in a single-center, urban academic tertiary care medical center retrospective cohort study.
2 The study center had a preexisting PDP protocol in place with prefilled labeled syringes available in the emergency department (ED) and intensive care unit (ICU) containing phenylephrine (100 μg/mL, 10mL) and epinephrine (10 μg/mL) for adult patients with hypotensive episodes.
Exclusion criteria included pregnancy, phenylephrine use for epistaxis or priapism, use in the operating room or ancillary procedural area, and patients with missing vital sign data within 60 minutes before PDP administration. Patients receiving both phenylephrine and epinephrine were also excluded. The primary outcome, efficacy, was defined as a 25% increase in systolic blood pressure (SBP) after PDP administration. Patients were divided into two cohorts: responders (≥ 25% increase in SBP) and nonresponders (<25% increase in SBP).
Secondary outcomes focused on safety, including hypertension (blood pressure >180/110 mm Hg within 60 minutes after receiving PDP), bradycardia (heart rate < 60 beats/min within 60 minutes after receiving phenylephrine), and tachycardia (heart rate increase by at least 30% from baseline within 60 minutes after receiving epinephrine).
The authors also looked at cardiac arrest within six hours after PDP administration, ICU and hospital length of stay (LOS), in-hospital mortality, extravasation, and severe adverse events (defined as severe bradycardia or hypertension requiring treatment). Notably, the study center PDP protocol included using epinephrine for patients with known cardiac dysfunction (ejection fraction < 40%) and phenylephrine for all other patients.
A total of 1727 patients were included in the study. The epinephrine group comprised 123 patients and the phenylephrine group comprised 1604 patients. Patient characteristics and efficacy outcomes were compared between responders and nonresponders within each group based on which PDP was administered. In the phenylephrine group, responders were older, had higher Acute Physiology and Chronic Health Evaluation (APACHE) II scores, and received less inotropes than nonresponders. Interestingly, more phenylephrine nonresponders had hypertension requiring IV treatment than did responders, indicating that PDP was unlikely responsible for the hypertension.
There was no difference in hospital mortality between responders and nonresponders. ICU and hospital LOS were longer in responders (8 and 14.5 days, respectively, P = 0.007) than in nonresponders (9 and 17 days, respectively, P = 0.001). In the epinephrine group, responders were more commonly White than other ethnicities and had higher APACHE II scores. There were no severe adverse events and no differences in cardiac arrest and ICU and hospital LOS.
This study had many limitations inherent in its retrospective design, such as a lack of specific documentation of the potential causes of hypotension, which could have bearing on PDP responsiveness. Of the 3175 patients who were screened, a surprising 1348 were excluded because they had received PDP in the operating room. The epinephrine group was smaller than the phenylephrine group despite epinephrine being used equally to, if not more than, other institutions as a PDP.
Baseline heart rates were not recorded in the study, and hypotensive patients without tachycardia could receive a dual benefit from the chronotropic and vasoconstrictor effect of epinephrine. Data regarding ventricular dysrhythmia linked to PDP use were omitted because these data were not available in the electronic medical record. This omittance was problematic because it is one of the biggest concerns in the ICU population.
The biggest limitation was the link between crystalloid bolus responsiveness and lack of phenylephrine response, but the authors were unable to capture the patients’ volume status, which would be one of the first things assessed in a hypotensive ED patient.
This study highlights the safety of using PDPs outside an operating room setting when there is a protocol in place with readily available, labeled, prefilled syringes. Future studies should be conducted in a prospective manner to identify any clinically significant outcomes when using different PDP medications and perhaps targeting etiologies of hypotension.
References
- Panchal AR, Satyanarayan A, Bahadir JD, Hays D, Mosier J. Efficacy of bolus-dose phenylephrine for peri-intubation hypotension. J Emerg Med. 2015 Oct;49(4):488-494.
- Singer S, Pope H, Fuller BM, Gibson G. The safety and efficacy of push dose vasopressors in critically ill adults. Am J Emerg Med. 2022 Nov;61:137-142.
