Is Vasopressin the near perfect pressor?

Is Vasopressin the near perfect pressor?

It isn’t often I have had the pleasure of reviewing a paper from my own center (maybe because I have been reticient to critique my colleagues) but this paper I couldn’t resist. If my colleagues are reading this then I will provide a spoiler alert that I am not planning on trashing the paper. A few years ago my colleague Dr. Yasser El Sayed (who many of you will know from his work on targeted echocardiography and ultrasound and most recently on www.pocusneo.ca) began touting the benefits of vasopressin as an inotrope. I have to confess, my knowledge of the drug was mostly at that point as a molecule that helps regulate water balance at the level of the kidney. As the saying goes you can’t teach an old dog new tricks so I suppose it has taken me some time to get around to embracing the other benefits of vasopressin. As an inotrope it has some interesting properties. It is through action on two different receptors that the appeal of this medication is derived. Firstly it acts on V1 receptors of blood vessels, causing vasoconstriction on the systemic side and supporting blood pressure and almost paradoxically in the lung at the same receptors, causes pulmonary vasodilation mediated by the endothelial release of nitric oxide. In the kidneys, as mentioned above it helps in water reabsorption through its action on V2 receptors. In other words it supports both the systemic and pulmonary vascular systems and maintains intravascular volume by preventing hypovolemia. That is a drug with some interesting properties.

Case Series From Winnipeg

One of our previous fellows Thomas Budniok authored Effect of Vasopressin on Systemic and Pulmonary Hemodynamics in Neonates along with Dr. El Sayed and Dr. Deepak Louis. This was a retrospecitve case series from 2011-2016 looking at patients who received vasopressin and I am delighted to say I cared for many of these babies so saw firsthand how the drug worked. The drug was typically used as a second or third line agent for hypotension and would be also be used when pulmonary hypertension complicated systemic shock as well (in addition to use of iNO). To look at the effect of vasopressin on hemodynamics, the authors used a previously validated score called the vasoactive inotropic score (VIS) = dopamine dose (μg/kg/min) + dobutamine dose (μg/kg/min) + 100 X epinephrine dose (μg/kg/min) + 10 X milrinone dose (μg/kg/min) + 10,000 X VP dose (U/kg/min) + 100 X norepinephrine dose (μg/kg/min). By looking at changes over time this gives an impression of the effect of the drug on other inotropic requirements. The authors looked at 33 episodes in 26 patients with a median starting dose was 0.3 mU/kg/min (IQR: 0.2–0.5).

The Results

While the starting dose was 0.3 mU/kg/min , the maximum dose was 0.65mU/kg/min (IQR: 0.4–1.2) with a duration of therapy of 37 hours (IQR: 21–69).

As you can see from the first figure of the paper, mean, systolic and diastolic blood pressures all rose over time. Might this be though that the infants were just getting better or we were using other inotropes to get the effect? Also as the measurements were taken at baseline and then 6,12 and 24 hours the influence of other measures might be expected to be less but it is the VIS that may yield more information.

Maybe not surprisingly, given the changes in blood pressure the following benefits to lactate and pH were also noted.

The VIS scores declined from 15 (9–20) to 13 (7–20) and 10 (8–16) at 24 and 48 hours post starting of vasopressin. Although not signficant, the median number of inotropes in use went from 2 to 1 after 24 hours.

As good as the medication seems to be the authors noted hyponatremia in in 21 episodes (64%) with severe hyponatremia in 7 episodes (33%). Personally I can comment that I stopped vasopressin myself in a couple patients due to this complication.

Final Thoughts

I suppose it goes without saying that future studies will need to look at vasopressin using a control group. Having said that I do believe this study provides some decent evidence of effect. The short time frame of analysis and the significant changes in hemodynamics and markers of perfusion with a reduction in dosing of additional inotropes suggests a decent effect of this drug. If you choose to use this medication however what prevents this from being the “perfect pressor” is the limitation of possible hyponatremia with its use. Hyponatremia though may be seen with higher doses so I suppose the saying may apply that with vasopressin a little may go a long way!

Integrated Evaluation of Hemodynamics

Integrated Evaluation of Hemodynamics

Welcome to the home page for our Integrated Evaluation of Hemodynamics program at the University of Manitoba. This program began in Winnipeg, Manitoba, Canada in 2014 and has been growing ever since.

What is considered normal hemodynamics?

1. Intact or normal hemodynamics implies blood flow that provides adequate oxygen and nutrient delivery to the tissues.

2. Blood flow varies with vascular resistance and cardiac function; both may be reflected in blood pressure(2). Normal cardiovascular dynamics should be considered within the context of global hemodynamic function, with the aim of achieving normal oxygen delivery and end organ performance

3. The current routine assessment of hemodynamics in sick preterm and term infants is based on incomplete information. We have addressed this by adopting an approach utilizing objective techniques, namely integrating targeted neonatal echocardiography (TNE) with near-infrared spectroscopy (NIRS). Implementation of these techniques requires an individual with the requisite TNE training, preferably in an accredited program, who also has a good understanding of perinatal and neonatal cardiovascular, respiratory, and other specific end organ physiology.

Why are premature infants more susceptible to cardiovascular compromise?

Hemodynamic compromise in the early neonatal period is common and may lead to unfavorable neurodevelopmental outcome4. A thorough understanding of the physiology of the cardiovascular system in the preterm infants, influence of antenatal factors, and postnatal adaptation is essential for the management of these infants during the early critical phase5. The impact of the various ventilator modes, the presence of a patent ductus arteriosus (PDA), and systemic inflammation all may affect the hemodynamics6. The poor clinical indicators of systemic perfusion and the relative insensitivity of conventional echocardiographic techniques in assessing myocardial contractility mean that monitoring of the hemodynamics of the preterm infant remains a challenge7.
What is integrated hemodynamics in neonatal care?

Integrated hemodynamics focuses on how to interpret multiple tools of hemodynamics evaluation in sick infants (TNE, clinical details, NIRS, organ specific ultrasound) and the art of formulating a pathophysiologic relevant medical recommendation.
Main objectives of applying Targeted Neonatal Echocardiography and Evaluation of Neonatal hemodynamics

Optimise care of infants with hemodynamic compromise to prevent progression into late irreversible stages of shock (Hypoxia)
Decrease overall PDA related complications (Hypoxemia and hypoxia)
Optimize care of infants with hypoxemic respiratory failure (HRF)
Decrease the incidence of progression of infants with hypoxemic respiratory failure and shock to end organ dysfunction

Objective of the program

Orientation to the hemodynamics concepts and basics

Orientation to the 3 level of the pathophysiologic approach to hemodynamics:

Level one: Relying on blood pressure trends (systole, diastole, and pulse pressure) and waveforms with other clinical parameters (all NICU practitioners)

Level one plus (advanced monitoring): Relying on blood pressure trend and near infrared spectroscopy (NIRS) for assessment of hemodynamics and oxygen extraction (optional to NICU practitioners)

Level two (TNE approach): Relying on both clinical parameters and TNE for objective assessment of cardiac output, extra and intra cardiac shunts, systemic and pulmonary vascular resistance. (Neonatologist trained on TNE)

Level three (integrated evaluation of hemodynamics): integrating blood pressure trends, TNE and NIRS for assessment of oxygen delivery, specific end organ oxygen consumption and the degree of compensation (comprehensive hemodynamic approach)

Understanding the rationale for the measurements and the specific values for each disease, and recognize limitations of the 3 models

To see research that we have done in the area of Integrated Hemodynamics please see our publication list that can be found here.

To access our video series providing examples of TNE and presentations on the use of hemodynamics in clinical application please see our Youtube channel playlist “Integrated Neonatal Hemodynamics”

References

Wolff CB. Normal cardiac output, oxygen delivery and oxygen extraction. Adv Exp Med Biol. 2008;599:169-182. doi:10.1007/978-0-387-71764-7-23.
Azhan A, Wong FY. Challenges in understanding the impact of blood pressure management on cerebral oxygenation in the preterm brain. Front Physiol. 2012;3 DEC(December):1-8. doi:10.3389/fphys.2012.00471.
de Boode WP. Clinical monitoring of systemic hemodynamics in critically ill newborns. Early Hum Dev. 2010;86(3):137-141. doi:10.1016/j.earlhumdev.2010.01.031.
Sehgal A. Haemodynamically unstable preterm infant: an unresolved management conundrum. Eur J Pediatr. 2011;170(10):1237-1245. doi:10.1007/s00431-011-1435-4.
Vutskits L. Cerebral blood flow in the neonate. Paediatr Anaesth. 2014;24(2):22-29. doi:10.1111/pan.12307.
Noori S, Stavroudis T a, Seri I. Systemic and cerebral hemodynamics during the transitional period after premature birth. Clin Perinatol. 2009;36(4):723-36, v. doi:10.1016/j.clp.2009.07.015.
Elsayed YN, Amer R, Seshia MM. The impact of integrated evaluation of hemodynamics using targeted neonatal echocardiography with indices of tissue oxygenation: a new approach. J Perinatol. 2017. doi:10.1038/jp.2016.257.