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.
When I think back to my early days as a medical student, one of the first lessons on the physical exam involves checking central and peripheral perfusion as part of the cardiac exam. In the newborn to assess the hemodynamic status I have often taught that while the blood pressure is a nice number to have it is important to remember that it is a number that is the product of two important factors; resistance and flow. It is possible then that a newborn with a low blood pressure could have good flow but poor vascular tone (warm shock) or poor flow and increased vascular tone (cardiogenic shock or hypovolemia). Similarly, the baby with good perfusion could be in septic shock and be vasodilated with good flow. In other words the use of capillary and blood pressure may not tell you what you really want to know.
Is there a better way?
As I have written about previously, point of care ultrasound is on the rise in Neonatology. As more trainees are being taught the skill and equipment more readily available opportunities abound for testing various hypotheses about the benefit of such technology. In addition to my role as a clinical Neonatologist I am also the Medical Director of the Child Health Transport Team and have pondered about a future where ultrasound is taken on retrievals to enhance patient assessment. I was delighted therefore to see a small but interesting study published on this very topic this past month. Browning Carmo KB and colleagues shared their experience in retrieving 44 infants in their paper Feasibility and utility of portable ultrasound during retrieval of sick preterm infants. The study amounted to a proof of concept and took 7 years to complete in large part due to the rare availability of staff who were trained in ultrasound to retrieve patients. These were mostly small higher risk patients (median birthweight, 1130 g (680–1960 g) and median gestation, 27 weeks (23–30)). Availability of a laptop based ultrasound device made this study possible now that there are nearly palm sized and tablet based ultrasound units this study would be even more feasible now (sometimes they were unable to send a three person team due to weight reasons when factoring in the ultrasound equipment). Without going into great detail the measurements included cardiac (structural and hemodynamic) & head ultrasounds. Bringing things full circle it is the hemodynamic assessment that I found the most interesting.
Can we rely on capillary refill?
From previous work normal values for SVC flow are >50 ml/kg/min and for Right ventricular output > 150 ml/kg/min. These thresholds if not met have been correlated with adverse long term outcomes and in the short term need for inotropic support. In the absence of these ultrasound measurements one would use capillary refill and blood pressure to determine the clinical status but how accurate is it?
First of all out of the 44 patients retrieved, assessment in the field demonstrated 27 (61%) had evidence using these parameters of low systemic blood flow. After admission to the NICU 8 had persistent low systemic blood flow with the patients shown below in the table. The striking finding (at least to me) is that 6 out of 8 had capillary refill times < 2 seconds. With respect to blood pressure 5/8 had mean blood pressures that would be considered normal or even elevated despite clearly compromised systemic blood flow. To answer the question I have posed in this section I think the answer is that capillary refill and I would also add blood pressure are not telling you the whole story. I suspect in these patients the numbers were masking the true status of the patient.
How safe is transport?
One other aspect of the study which I hope would provide some relief to those of us who transport patients long distance is that the head ultrasound findings before and after transport were unchanged. Transport with all of it’s movement to and fro and vibrations would not seem to put babies at risk of intracranial bleeding.
Where do we go from here?
Before we all jump on the bandwagon and spend a great deal of money buying such equipment it needs to be said “larger studies are needed” looking at such things as IVH. Although it is reassuring that patients with IVH did not have extension of such bleeding after transport, it needs to be recognized that with such a small study I am not comfortable saying that the case is closed. What I am concerned about though is the lack of correlation between SVC and RVO measurements and the findings we have used for ages to estimate hemodynamic status in patients.
There will be those who resist such change as it does require effort to acquire a new set of skills. I do see this happening though as we move forward if we want to have the most accurate assessment of clinical status in our patients. As equipment with high resolution becomes increasingly available at lower price points, how long can we afford not to adapt?
Thank you to Dr El-Sayed for providing slides and a great deal of guidance in developing this post!
I am too young a Neonatologist to recall some of the changes in practice that would be considered giant leaps in my field. Provision of antenatal steroids to accelerate lung maturity, development of ventilators and provision of surfactant to premature infants have saved millions of lives the world over and reduced morbidities from the conditions they were designed to treat.
I believe we are embarking on another such tidal wave of change that is beginning to take shape and will come crashing into the shores of our practices globally before long. What makes it all the more exciting is that I have a front row seat to view the birth of this development. The story begins over a decade ago with the understanding that traditional echocardiograms as performed by a Cardiologist in some instances could not provide us as Neonatologists with enough information to guide clinical decision making. Let me state up front that the program I will be discussing would not be possible without the participation of our colleagues in Cardiology and moreover the information that they provide for many infants with congenital heart disease is critical to our practice. What I am referring to though are those instances where we are more interested in the flow of blood or the function of the heart in the presence of a structurally normal heart.
In Canada there is no doubt that Dr. Patrick McNamara has been a pioneer in the field of Targeted Neonatal Echocardiography (TNE) and has published extensively in the field. One such paper from 2009 highlights how TNE can be of use in the treatment of a PDA. TNE though has expanded in use to guide treatment of such conditions as PPHN with or without BPD, heart failure, shock and also point of care functions such as determination of line placements or intravascular clots. Additional work has been done by pioneers in Australia such as Nick Evans. We were very fortunate to have Dr. Yasser El-Sayed train under Dr. McNamara and then return to Winnipeg to develop our own clinical program for TNE in consultation with our colleagues in Pediatric Cardiology.
Since it’s inception here the program has been utilized extensively with clinical management in many cases influenced by the findings. We believe though that our program may be unique in the sense that the philosophy of using this technology is only as part of a larger framework as outlined in this figure. The program is known as Integrated Evaluation of Neonatal Hemodynamics (INEH). The concept is that we cannot rely on only one measure of cardiac performance or blood flow patterns. Rather it is through consideration of six separate streams of data that we can come to an accurate conclusion. For example a patient who is hypotensive as defined by a mean blood pressure lower than their gestational age but who has adequate cerebral blood flow as measured by Near Infrared Spectroscopy, normal SVC flow and contractility, as a measure of cardiac performance with a normal lactate and urine output, may need simple observation. Why treat with an inotrope if the end organs are not impaired in the least?
How do we accomplish this is practice? The integration is done by using data as shown in the next figure. Markers such as NIRS, lactate, BNP, indwelling arterial access, urine output all provide useful markers which are integrated to determine the best course of action.
I would like to provide an illustrative case. The patient in this presentation is one who developed hypoxic ischemic encephalopathy. If you read through the slides you will clearly see how the use of INEH brought about a significant change in the approach to the care of the infant. Without this information we would have continued to go down a treatment path which was not addressing the issues at hand appropriately. Please click on the link to view this presentation.
I am proud to say that Dr. El-Sayed is spreading this message and approach globally having recently given workshops in Turkey and Egypt. We are also very excited that in the Fall from October 29th – 31st we will be hosting the 10th Annual Bowman Symposium featuring Neonatal Hemodynamics. For more information please click here.
The importance of this approach to Neonatal Care can not be emphasized enough. With so many needs in our Health Region it is difficult to always obtain enough funds to purchase all the equipment that one needs for a service. As such I was grateful to Dr. El-Sayed for presenting such need at a recent charitable event as shown below!
If you or someone you know is interested in this emerging field we would love to hear from you. If you would like to attend the Bowman Symposium please contact us at: