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ORIGINAL ARTICLE
Year : 2020  |  Volume : 9  |  Issue : 1  |  Page : 52-56

A Study of reversal of diastolic blood flow in the middle cerebral artery using doppler ultrasound in the prognostication in sick neonates


1 Consultant Neonatologist, Department of Neonatology, Manipal Hospital, Bengaluru, Karnataka, India
2 DNB Neonatology Trainee, Department of Neonatology, Manipal Hospital, Bengaluru, Karnataka, India

Date of Submission26-Jul-2019
Date of Decision19-Oct-2019
Date of Acceptance22-Dec-2019
Date of Web Publication29-Jan-2020

Correspondence Address:
Dr. Iyer Harohallli Venkatesh
Manipal Hospital, Bengaluru, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcn.JCN_83_19

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  Abstract 


Background: The cerebral circulation is maintained on the principle of brain uniqueness cerebral autoregulation. Many factors such as oxygen, carbon dioxide, and blood pressure play a major role in the smooth journey of cerebral circulation. There is no clear marker used to assess the impending mortality in sick neonates. The resistive index (RI) is a measure of pulsatile blood flow, reflecting the resistance to flow caused by microvascular bed. The RI of the cerebral vessels is used to know the amount of blood that is flowing in the brain. Increased cerebral blood flow reduces the RI and decreased flow increases the resistance and the brain stays between the two, and hence, the autoregulation is maintained. When the cerebral autoregulation is lost, the flow in the diastole reverses and helps in the prognostication. Objective and Design: A prospective cohort study was conducted between March 2017 and May 2018 catering to both inborn and outborn neonates at Manipal Hospital, Bengaluru, to determine the importance of reversal of diastolic flow of RI in the middle cerebral artery as a marker of mortality in sick neonates. Subjects and Interventions: We enrolled 22 sick neonates both term and preterm. Normal resistive indices in neonates were taken as 0.6–0.9. Method: The RI was manually assessed in the middle cerebral artery using pulsed-wave Doppler. The mean RI was calculated from the average peak systolic velocity and end-diastolic velocity of at least five sequential stable waveforms. The reversal of diastolic flow in the RI was determined by the retrograde flow of waveform during diastole. Univariate and multivariate analyses were performed to identify prognostic factors for the overall survival, which was depicted using Kaplan–Meier curve.P< 0.05 was considered statistically significant. Results: Neonates who had a reversal of diastolic flow had a poor mean survival of 1.3 h when compared to those patients who did not have a reversal of flow of 133.8 days (hazard ratio [HR] – 4.66; 95.% confidence interval [CI]: 1.250–16.96) which was statistically significant (P = 0.022). Furthermore, birth weight <1000 g had a mean survival of 29 days, whereas birth weight >2500 g had a mean survival of 104 days (HR – 0.96; 95% CI: 0.460–2.032) which also was statistically significant (P < 0.001). Conclusion: As determined by univariate and multivariate analyses, the reversal of diastolic flow in the cerebral artery can strongly be used as a surrogate marker for impending mortality in a sick neonate.

Keywords: Cerebral blood flow, prognosis, sick neonate


How to cite this article:
Venkatesh IH, Shubha H V, Karthik N, RaviShankar S. A Study of reversal of diastolic blood flow in the middle cerebral artery using doppler ultrasound in the prognostication in sick neonates. J Clin Neonatol 2020;9:52-6

How to cite this URL:
Venkatesh IH, Shubha H V, Karthik N, RaviShankar S. A Study of reversal of diastolic blood flow in the middle cerebral artery using doppler ultrasound in the prognostication in sick neonates. J Clin Neonatol [serial online] 2020 [cited 2020 Feb 25];9:52-6. Available from: http://www.jcnonweb.com/text.asp?2020/9/1/52/277231




  Introduction Top


Cerebral blood flow (CBF) autoregulation is of paramount importance in maintaining cerebral circulation in sick neonates. Once this is lost, there is an initial increase in the resistive index (RI) followed by a reversal of flow when the neuronal tissue begins to die. The pathogenesis of several neuropathological injuries in the neonatal period is related to CBF impairment, but most of the methods used to assess CBF are technically complex, invasive, or costly. Doppler ultrasonography has been used in several studies to determine CBF velocity in intracranial cerebral arteries of asphyxiated newborns.[1] Cerebral vascular anatomy and disturbance of cerebral hemodynamics are key factors in the pathophysiology of brain injury. Therefore, there is renewed interest in noninvasive methods to evaluate CBF. One such method assessing one aspect of CBF is measuring the RI in the cerebral arteries using color Doppler imaging. The internal carotid artery, basilar artery, anterior cerebral artery, and lenticulostriate arteries can be easily visualized with color Doppler imaging. The RI has been used to detect intracranial abnormalities including asphyxia, cerebral edema, hydrocephalus, and brain death,[2] and also, low RI is considered a possible sign of luxury perfusion in term birth asphyxia,[3] but not much of the literature found to assess the mortality in sick neonates. Here, we have tried to analyze the role of reversal of RI in sick neonates as a marker for impending mortality.


  Methods Top


A prospective cohort study was conducted between March 2017 and May 2018 in a tertiary care center. We enrolled 22 sick neonates both term and preterm. Information regarding the birth weight, gestational age, gender, mode of delivery, and resuscitation details were collected after obtaining informed written consent. Neonates with major congenital anomalies were excluded from the study.

Infants were examined with cranial ultrasound, including color Doppler imaging. Ultrasound was performed on Philips CX50 using S 12-4 frequency footprint probe when there was deterioration in hemodynamics. Images were obtained in a transtemporal plane. The middle cerebral artery was visualized using color Doppler, and the RI was manually assessed in the aforementioned artery using pulsed-wave Doppler. The RI was defined as (S-D)/S where S is the height of the systolic peak and D is the height of the end-diastolic peak. Normal resistive indices in neonates were taken as 0.6–0.9 [Figure 1]. The reversal of diastolic flow in the central nervous system (CNS) was defined as antegrade flow into the CNS during systole and retrograde flow during diastole [Figure 2], which causes the resultant loss of tissue perfusion. The RI was manually assessed in the middle cerebral artery using pulsed-wave Doppler. The mean RI was calculated from average peak systolic velocity and end-diastolic velocity of at least five sequential stable waveforms. Data were collected using Microsoft (MS) Excel. Univariate and multivariate analyses were performed to identify prognostic factors for overall survival which was interpreted using Kaplan–Meier curve [Figure 3]. Cox regression, log-rank test, hazard ratio (HR), and confidence interval (CI) was calculated, and P value (probability that the result is true) of <0.05 was considered statistically significant after assuming all the rules of statistical tests. MS Excel using SPSS version 22 (IBM SPSS Statistics, Somers, NY, USA) statistical software was used to analyze the data.[3]
Figure 1: Pulse-wave Doppler of the middle cerebral artery demonstrating normal resistive index

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Figure 2: Pulse-wave Doppler of the middle cerebral artery demonstrating reversal of diastolic blood flow

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Figure 3: Kaplan–Meier for the reversal of diastolic flow

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  Results Top


Of the 22 neonates analyzed, 45% of the neonates were <28 weeks of gestation with a mean survival of 26.4 days, as compared to mean survival of 89.04 days in the gestation of more than 37 weeks. There was no statistical significance in gender distribution. There was no significant difference between the survival of small for gestational age or appropriate for gestational age neonates. Neonates who had a reversal of diastolic flow had a poor mean survival of 1.3 h when compared to those patients who did not have a reversal of flow of 133.8 days (HR – 4.66; 95% CI: 1.250–16.96) which was statistically significant (P = 0.001). Furthermore, birth weight <1000 g had a mean survival of 29 days, whereas >2500 g had a mean survival of 104 days. (HR – 0.96; 95% CI: 0.460–2.032), which also was statistically significant (P < 0.001) [Table 1]. Based on the reversal of diastolic flow, 31.8% of the neonates were <28 weeks and 36.3% were <1000 g [Table 2]. There was no statistical significance between gender, mode of delivery, or gestational age. The single most parameter which could signify mortality was a reversal of diastolic flow in the middle cerebral artery (HR – 3.00; 95% CI: 1.191–7.551), which was statistically significant (P = 0.001) [Table 3].
Table 1: The percentage of survival and the variables

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Table 2: Reversal of cerebral blood flow and the variables

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Table 3: The mortality and the variables

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  Discussion Top


The cerebral autoregulation is the brain's ability to maintain the constant flow of blood in the brain despite the variation in the perfusion pressure.[1] The unique architecture circle of Willis formed by two carotid arteries and two vertebral arteries at the base of the brain surface makes the blood supply to the brain. The normal CBF is 50 ml/100 g of the brain tissue/min.

Although the brain makes 2% of the total body weight, it receives 15% of resting cardiac output. The flow remains constant as long as the cerebral perfusion pressure is maintained between 60 and 160 mm of Hg keeping the cerebral autoregulation intact.

There are many factors such as the concentration of oxygen, carbon dioxide, and hydrogen ion concentration, and the factors released from the astrocytes regulate the flow of blood in the brain.[2],[3],[4],[5],[6],[7] The increased arterial carbon dioxide entering the brain causes the dilatation of cerebral vessels. The dissociation of carbonic acid formed by the combination of carbon dioxide and water in the brain releases the hydrogen ion, in turn, causing cerebral vasodilatation. Excess hydrogen concentration reduces the neuronal activity, and hence, increased vasodilatation would remove carbon dioxide and hydrogen ion away from the brain. The utility of oxygen in the brain plays a major role. The normal utilization of the brain is around 3.5 ml of oxygen per 100 g of the brain. If the blood flow is insufficient to deliver this needed amount of oxygen, the cerebral vasodilatation happens. The astrocytes covering the blood vessels in the brain release active metabolites such as nitric oxide, adenosine, and potassium ions in response to the stimulation of adjacent excitatory neurons, leading to the cerebral vasodilatation. In general, myogenic, neurogenic, metabolic, and endothelial are the four major mechanisms that play a crucial role in the maintenance of autoregulation. The alteration in the CBF and impaired autoregulation makes the brain vulnerable to the injury which might lead to neuronal death in neonates.

The preterms babies differ from that of the term with regard to the anatomy and circulation of the brain making them more vulnerable to the injury.[8],[9] The frequency of impaired autoregulation is associated with low gestational age and birth weight as well as systemic hypotension.

The pathological conditions such as intraventricular hemorrhage, subdural hematoma, cerebral edema, and patent ductus arteriosus in preterm neonates will contribute to decreased CBF, causing increased RI, and the cerebral infarct and perinatal asphyxia make the blood flow luxuriously with decreased RI.

The methods used to assess the CBF such as near-infrared spectroscopy[10] and diffusion correlation spectroscopy are not readily available in low-income resource-limited countries. The noninvasive bedside ultrasound is used to assess the CBF velocities, thereby correlating the results with neurological outcome.

The diastolic reversal of CBF indicates the loss of autoregulation which can be quantified using bedside Doppler ultrasound. Any cerebral vessel can be used in the measurement of CBF. In our study, we have used the middle cerebral artery to measure the velocity of blood flow for the ease to perform.

Any elevation of external pressure due to oligohydramnios or internal pressure due to hydrocephalus can cause of reversal of diastolic blood flow. In the majority of cases, the cause of this abnormal pattern is unknown.

According to our study, the lower the gestation, the lesser was the mean survival. This could be attributed to the fact that our study also included extreme preterm and extremely low birth weight admitted for comfort care, wherein no aggressive resuscitation was initiated.

Higher RI had an adverse outcome which was similar to Argollo et al.[11] The loss of anterograde flow in the middle cerebral artery was associated with the fatal outcome which was similar to a study by Glasier et al.[12]

The excessive transducer pressure created while performing the Doppler ultrasound causes a transient reversal of blood flow. In our cases, utmost care was taken to avoid pressure over the scalp.

The strength of this study was assessing the cerebral blood through ultrasound Doppler which can help prognosticate illness in sick neonates. The limitation of the study was that a small cohort was analyzed and more such studies are required before it can be used as a single sign for impending death.

Therefore, RI can be used as a surrogate marker for impending mortality and becomes an important parameter to assess in sick neonates.


  Conclusion Top


In an era of the dilemma of diagnosis of fatal outcome in sick neonates, we conclude that the reversal of diastolic flow in the cerebral artery can be used as a surrogate marker to assess the impending mortality in sick neonates.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Paulson OB, Strandgaard S, Edvinsson L. Cerebral autoregulation. Cerebrovasc Brain Metab Rev 1990;2:161-92.  Back to cited text no. 1
    
2.
Masamoto K, Tanishita K. Oxygen transport in brain tissue. J Biomech Eng 2009;131:074002.  Back to cited text no. 2
    
3.
Reivich M. Arterial PCO2 and cerebral hemodynamics. Am J Physiol 1964;206:25-35.  Back to cited text no. 3
    
4.
Kety SS, Schmidt CF. The effects of altered arterial tensions of carbon dioxide and oxygen on cerebral blood flow and cerebral oxygen consumption of normal young men. J Clin Invest 1948;27:484-92.  Back to cited text no. 4
    
5.
Drake CT, Iadecola C. The role of neuronal signaling in controlling cerebral blood flow. Brain Lang 2007;102:141-52.  Back to cited text no. 5
    
6.
Rennels ML, Nelson E. Capillary innervation in the mammalian central nervous system: An electron microscopic demonstration. Am J Anat 1975;144:233-41.  Back to cited text no. 6
    
7.
Osol G, Brekke JF, McElroy-Yaggy K, Gokina NI. Myogenic tone, reactivity, and forced dilatation: A three-phase model of in vitro arterial myogenic behavior. Am J Physiol Heart Circ Physiol 2002;283:H2260-7.  Back to cited text no. 7
    
8.
Rorke LB. Anatomical features of the developing brain implicated in pathogenesis of hypoxic-ischemic injury. Brain Pathol 1992;2:211-21.  Back to cited text no. 8
    
9.
Wong FY, Leung TS, Austin T, Wilkinson M, Meek JH, Wyatt JS, et al. Impaired autoregulation in preterm infants identified by using spatially resolved spectroscopy. Pediatrics 2008;121:e604-11.  Back to cited text no. 9
    
10.
Kainerstorfer JM, Sassaroli A, Tgavalekos KT, Fantini S. Cerebral autoregulation in the microvasculature measured with near-infrared spectroscopy. J Cereb Blood Flow Metab 2015;35:959-66.  Back to cited text no. 10
    
11.
Argollo N, Lessa I, Ribeiro S. Cranial Doppler resistance index measurement in preterm newborns with cerebral white matter lesion. J Pediatr (Rio J) 2006;82:221-6.  Back to cited text no. 11
    
12.
Glasier CM, Seibert JJ, Chadduck WM, Williamson SL, Leithiser RE Jr. Brain death in infants: Evaluation with Doppler US. Radiology 1989;172:377-80.  Back to cited text no. 12
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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