It gives me great pleasure to write this piece as it is about research that two of my colleagues Dr. Yasser Elsayed and Dr. Shyamala Dakshinamurti authored along with colleagues in Saudi Arabia. Both colleagues have worked in the fields of hemodynamics and pulmonary hypertension for some time. For those of you who know Yasser you would know that he has had an interest in what one can glean from careful attention to a patient monitor for some time. In fact we created some short Youtube videos on these topics a few years ago that are available on the accompanying Youtube channel to this site.
What if you don’t have ready access to an ECHO?
If you are like me, you are blessed to work in a centre that has easy access to evaluation of hemodynamics. What if you are in a centre that doesn’t have such access? Alternatively, in the spirit of using resources wisely what if you don’t want to exhaust your hemodynamics team by asking them to assess every murmur that comes along in a preterm infant. In other words, is there a way to tell whether a ductus is hemodynamically significant or not? There is a lot of preceding research that would tell us that our stethescope and fingertips are not as accurate as we would like to think in determining which ducts are likely significant, if open at all.
In comes the pulsatility index. The pulsatility index is derived from the formula;
(peak systolic velocity – end diastolic velocity) /mean velocity
Moreover, this value can be obtained using an oxygen saturation probe based on the absorption of light by pulsatile and non-pulsatile tissues. Patient monitors can express this number with > 2 being higher than the upper limit of normal in preterm infants, 1–2 being normal, 0.4–1 being low normal, and < 0.4 low PI. The patient monitor moreover is capable of providing histograms for this data providing the user with a bar graph indicating the percentage of time over twenty four hours that the infant has been in each of these ranges. Osman AA et al used this information to study the relationship between PI in the periods of time before an infant develops a HS PDA, during treatment and afterwards in their paper The perfusion index histograms predict patent ductus arteriosus requiring treatment in preterm infants. They studied 34 preterm infants in four time periods, namely 24 h before starting treatment of PDA, during PDA treatment, and 24 h after completion of the course of treatment, and confirmed PDA closure by echo. The data was obtained from a oxygen saturation probe placed on the right wrist in a preductal location. They also compared PI during matched time periods in infants without a HS PDA in order to determine what the PI ranges would be for patients of a matched gestational age without a ductal concern.
For the ECHO diagnosis of a HS PDA they used the following criteria:
A ductal diameter at the pulmonary side ≥ 1.5 mm and at least one of the following:
Before the PDA was treated but was identified as being significant the figure below shows that the incidence of low flows were statistically more likely to be present ini HS PDA. This remained true during treatment with a stabilization follwoing treatment.
The authors examined the best predictive findings from the histogram analysis and discovered that “presence of a PI <0.4 for > 10% of the recorded time, together with the presence of a PI > 2 for > 8% of the time recorded, is predictive of a PDA requiring treatment, with a sensitivity and specificity of 77 and 96%; positive and negative predictive values of 94 and 81%, respectively;and an area under the curve of 0.88 (95% confidence interval 0.78–0.95, p = 0.004)”
How do we explain this in terms of physiology? The low flow state I think is the easier one to think about. If you have a HS PDA blood is “stolen” from the aorta and is directed to the lungs. This stolen flow may lead to lower perfusion than normal to the distal extremities as aortic flow is less than what it normally would be. Therefore with less flow in a vessel the pulsatility index declines. How then could you find a high PI in the same patient? The situation may arise if there is intermittent hypoxia that increases pulmonary vascular resistance thereby lessening the flow and restoring good flow in the aorta. The combination therefore was found to be predictive of a HS PDA with a reasonable specificity in particular. If you don’t have a low PI it is unlikely you have a HS PDA.
How could we use this?
Don’t worry I am not going to suggest that we can do away with the hemodynamics assessment. I do wonder though if this information could be very useful in helping to triage resources when they may be quite limited. In other words, if you hear on morning report that a 27 week infant has become tachypneic and has a murmur, instead of jumping to call the Hemodynamics service why not check the 24 hour PI histogram? If you don’t see low flows it is unlikely as I read this that a HS PDA is present. To be clear I am not saying that I am totally sold on this! I think it needs to be recognized this was a small study and will need further larger samples to confirm as there would be more babies with varying levels of PDAs in terms of hemodynamics to study. In the meantime though I think it would be very interesting to take a look at the 24 hour PI histograms for the next number of babies I see and look at how it does correlate with the ECHO I ask for. No doubt as two of the authors in the paper work with me I won’t have to remember this post to check the values as I am sure this is not the last I will hear of this!
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).
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.
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!
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”
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.