Published online October 2, 2006
PEDIATRICS Vol. 118 No. 4 October 2006, pp. 1456-1466 (doi:10.1542/peds.2006-0661)
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ARTICLE

Hemodynamic Changes After Low-Dosage Hydrocortisone Administration in Vasopressor-Treated Preterm and Term Neonates

Shahab Noori, MDa, Philippe Friedlich, MDa, Pierre Wong, MDb, Mahmood Ebrahimi, MDa, Bijan Siassi, MDa,b and Istvan Seri, MD, PhDa

a Divisions of Neonatal Medicine
b Cardiology, Department of Pediatrics, Childrens Hospital Los Angeles and Women's and Children's Hospital, LAC+USC Medical Center, Keck School of Medicine, University of Southern California, Los Angeles, California


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
OBJECTIVE. We sought to investigate whether the increase in blood pressure and decrease in vasopressor support after hydrocortisone administration are associated with changes in systemic hemodynamics in neonates who receive high-dosage dopamine to maintain blood pressure at the lowest acceptable levels.

METHODS. In this prospective, observational study, preterm and term neonates who required dopamine ≥15 µg/kg per minute to maintain minimum acceptable blood pressure received intravenous hydrocortisone 2 mg/kg followed by up to 4 doses of 1 mg/kg every 12 hours. Fifteen preterm and 5 term neonates without a patent ductus arteriosus composed the study population. Echocardiograms and vascular Doppler studies were performed immediately before the first dose of hydrocortisone and at 1, 2, 6 to 12, 24, and 48 hours thereafter.

RESULTS. In the 15 preterm infants, during the first 12 hours of hydrocortisone treatment, the 28% increase in blood pressure paralleled that in the systemic vascular resistance without changes in stroke volume or cardiac output, whereas dopamine dosage decreased. By 24 hours, the dosage of dopamine continued to decrease, whereas stroke volume increased without additional changes in systemic vascular resistance. By 48 hours, dopamine dosage decreased by 72%; blood pressure and stroke volume increased by 31% and 33%, respectively; and systemic vascular resistance and cardiac output tended to be higher (14% and 21%, respectively) compared with baseline. Contractility, global myocardial function, and Doppler indices of blood flow in the middle cerebral and renal artery remained normal and unchanged. The findings in the 5 term infants showed a similar pattern for changes in cardiac function, systemic hemodynamics, and organ blood flow after hydrocortisone administration.

CONCLUSIONS. In preterm and term neonates who require high-dosage dopamine to maintain blood pressure at the lowest acceptable levels, hydrocortisone improves blood pressure without compromising cardiac function, systemic perfusion, or cerebral and renal blood flow.

Key Words: preterm • blood pressure • cardiac function • brain blood flow • dopamine

Abbreviations: CBF—cerebral blood flow • BP—blood pressure • SVR—systemic vascular resistance • PDA—patent ductus arteriosus • MPI—myocardial performance index • SF—shortening fraction • WS—wall stress • VCFC—heart rate–corrected velocity of circumferential fiber shortening • VTI—velocity time integral • MCA—middle cerebral artery • MV—mean velocity • PI—pulsatility index • ANOVA—analysis of variance

Severe and prolonged hypotension and impaired cerebral blood flow (CBF) and CBF autoregulation1–3 are associated with increased mortality and central nervous system morbidity in critically ill preterm and term infants.4–7 Therefore, attempts have been made to determine whether interventions that lead to normalization of blood pressure (BP), cardiac output, and organ perfusion improve mortality and short- and long-term central nervous system morbidity in this patient population.8–11

In most hypotensive infants, cautious volume administration and the early use of low to medium dosages of dopamine1,9,12 or epinephrine8 are effective in stabilizing the cardiovascular status and renal function. However, a subgroup of hypotensive preterm and term infants do not respond to low to medium dosages of vasopressor inotropes. These patients require high dosages of dopamine often in combination with epinephrine and/or dobutamine to maintain BP in the perceived reference range or do not respond at all and develop vasopressor-resistant hypotension.9,13,14 Although the pathophysiology of vasopressor resistance has not been clarified fully, downregulation of the cardiovascular adrenergic receptors during critical illness and exogenous catecholamine administration15,16 as well as relative or absolute adrenal insufficiency17–23 have emerged recently as probable causative factors.

In critically ill preterm and term infants with vasopressor resistance, low-dosage steroid administration has been shown repeatedly to improve BP and renal function.13,17,18,24–27 Recent findings also have revealed that in preterm infants, BP increases by 2 hours after the first dose of steroid treatment, whereas vasopressor inotrope requirement decreases by 6 to 12 hours of steroid administration.17,24 Although the mechanisms of these cardiovascular effects of steroid administration are not understood completely, both genomic and nongenomic steroidal effects seem to play a role.17,28–30

BP is the result of the interaction between cardiac output and systemic vascular resistance (SVR). Therefore, in theory, the increase in BP after steroid administration could be attributable to an increase in cardiac output, SVR, or both. However, when the myocardium is immature and/or injured and high dosages of vasopressors without careful titration are being administered, cardiac output and systemic perfusion may decrease in the face of the elevated SVR while the clinician may be reassured by the improvement in BP. Because the myocardium of the neonate, especially that of the preterm infant, is very sensitive to increased afterload, an excessive rise in SVR could compromise cardiac output and decrease organ perfusion.31

Because dexamethasone treatment has potentially detrimental neurodevelopmental effects, especially in the preterm neonate,32 and because hydrocortisone administration also represents a hormone replacement therapy with more balanced gluco- and mineralocorticoid effects in patients with relative adrenal insufficiency,9,33 hydrocortisone has become the preferred corticosteroid to treat neonates with vasopressor resistance.13,17,21,27 The beneficial effects of low-dosage hydrocortisone in this patient population have been investigated only at the level of the changes in BP and urine output. Although the reported increase in urine output suggests that the improvement in BP after hydrocortisone administration likely is associated with improved organ blood flow,17,27 no study has studied systematically the effect of hydrocortisone on cardiac function, systemic hemodynamics, and organ blood flow. Because successful treatment of shock depends on normalization of organ blood flow and because BP does not reflect accurately the status of organ blood flow in neonates, especially in compensated shock,9,27–32 assessment of the hemodynamic status and organ blood flow in hydrocortisone-treated neonates is of importance. Therefore, in this prospective, observational study, we examined the effects of low-dosage hydrocortisone on cardiovascular function and organ blood flow in neonates with vasopressor resistance. It is important to note that we report on the changes in systemic hemodynamics that are associated with the increase in BP after hydrocortisone administration in neonates who were beyond the immediate postnatal transitional period, did not have a patent ductus arteriosus (PDA), and, by definition, were not in uncompensated shock as they had maintained minimally acceptable BP on high-dosage dopamine before the hydrocortisone treatment was initiated.


   METHODS
TOP
 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
This prospective, observational study was conducted from September 1, 2003, to September 30, 2005, at Childrens Hospital Los Angeles and the Women's and Children's Hospital of the LAC+USC Medical Center at the University of Southern California. The respective institutional review boards approved the study, and informed consent was obtained.

Patients were included when they presented with vasopressor resistance, had a postmenstrual age of ≤44 weeks, and had not been exposed to steroid treatment within 72 hours before enrollment and there was a plan to start hydrocortisone to treat vasopressor resistance per strict divisional guidelines. The minimum acceptable BP was defined by the attending neonatologist as BP values at or just above the 10th percentile of published BP norms.33,34 Patients were excluded when they had congenital heart defects or no parental consent could be obtained in a timely manner.

According to the divisional guidelines for the treatment of neonates with hypotension and cardiovascular instability, hypotensive neonates first receive a normal saline bolus of 10 to 20 mL/kg followed by a stepwise titration of dopamine infusion if they remain hypotensive. Dobutamine is added, and dopamine is attempted to be weaned if patients continue to be hypotensive on high dosages of dopamine (≥15–20 µg/kg per minute) and/or there is echocardiographic evidence of myocardial dysfunction. Hypotension is defined as mean BP at or below the 10th percentile for gestational and postnatal age–dependent norms.33,34 Vasopressor resistance generally is defined as a dopamine requirement of ≥15 µg/kg per minute with or without other vasoactive amines and/or inotropes to maintain the minimum acceptable BP. In patients with vasopressor resistance, hydrocortisone was started, and the course consisted of an initial intravenous dose of 2 mg/kg followed by 1 mg/kg intravenously every 12 hours up to 4 additional doses. The complete set of 4 additional doses was given only when the patient remained hypotensive or maintained only minimum acceptable BP with a dopamine dose of ≥5 to 8 µg/kg per minute when the next hydrocortisone dose was due.

Functional echocardiograms and organ blood flow Doppler studies were performed immediately before the first dose of hydrocortisone and at 1, 2, 6–12, 24, and 48 hours thereafter using a Philips (Andover, MA) SONOS 5500 ultrasound machine. Cardiovascular parameters that were measured/calculated included the left cardiac output, left stroke volume, SVR, myocardial performance index (MPI), shortening fraction (SF), wall stress (WS), heart rate–corrected velocity of circumferential fiber shortening (VCFc), and the z score of the VCFc-WS relation. An average of 3 measurements were used to calculate each value. Left cardiac output was calculated using the aortic diameter and velocity time integral (VTI) measured at the aortic valve annulus from parasternal long-axis and apical views, respectively. Cardiac output was calculated by a built-in software using the formula ({pi}D2/4) x VTI x heart rate. Left stroke volume was calculated by dividing the cardiac output by the heart rate. SVR was calculated using the formula SVR = (mean BP – right atrial pressure)/cardiac output. Right atrial pressure was estimated at 4 mmHg. The MPI, a measure of global myocardial function (both systolic and diastolic components) is the sum of the isovolumic contraction and relaxation times divided by the ejection time. Because it is inversely related to myocardial function, an increase in the MPI indicates worsening global myocardial function. We used the following formula to calculate the MPI: (A – B)/B, where A is the time span between the end of 1 mitral flow Doppler envelope to the beginning of the next envelope and B is the ejection time. Left ventricular systolic function was assessed by load-dependent and load-independent measures of systolic function such as the SF and the VCFC-WS relation measured by M-mode echocardiography,35 respectively. Finally, z scores of VCFc-WS relations were calculated.

Organ blood flow velocity measurements in the middle cerebral artery (MCA; temporal approach) and right renal artery (dorsolateral approach) were conducted with the transducer positioned at an angle of insonation of <10 degrees. For each artery, the peak systolic, end diastolic, and time-averaged mean velocities (MV) as well as the VTI were measured in at least 3 sequential homogeneous cardiac cycles of optimal quality. Pulsatility index (PI) was calculated using the formula PI = (peak systolic velocity – end diastolic velocity)/mean velocity. Because PI, MV, and VTI have been shown to correlate with changes in organ blood flow, they were used to assess the changes in organ blood flow after hydrocortisone administration.36–38 A decrease in the PI or an increase in the MV or VTI indicates increases in organ blood flow. It is of note that, because VTI is affected by changes in the heart rate, the usefulness of this relative measure of organ blood flow is limited when significant changes in heart rate occur.

BP was measured with an umbilical or peripheral arterial catheter connected to a pressure transducer. In patients with dampened arterial waveforms or in the absence of an arterial line, BP was measured by oscillometry using the average of 2 to 3 individual measurements for each data point. Urine output was calculated in 6-hour blocks before and after the first dose of hydrocortisone. Similarly, fluid balance was calculated 12 hours before and after the first dose of hydrocortisone. Data on the dosage of dopamine were collected during the study for all patients.

Statistical Analysis
Distribution of continuous variables was tested for normality. For normally distributed variables, equality of the means was tested by t test. For all other continuous variables, equality of distribution was tested by the Mann-Whitney test. Serial changes in cardiovascular parameters were analyzed using 1-way analysis of variance (ANOVA) for repeated measures and pairwise comparisons with adjustment for multiple comparisons (Bonferroni). Analysis of covariance was used to correct the effect of CO2 and hematocrit on the MCA flow. Values are given as mean ± SD unless noted otherwise. P < .05 was considered to indicate significance. Analyses were performed with SAS 9.1 (SAS Institute, Inc, Cary, NC).


   RESULTS
TOP
 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 CONCLUSIONS
 REFERENCES
 
During the study period, 23 patients met entry criteria and were enrolled. However, because 3 of the patients who initially were enrolled had a PDA and because PDA has significant effects on systemic and pulmonary hemodynamics, only the 20 neonates (15 preterm and 5 term) without a PDA were included in the analysis. Table 1 summarizes the clinical characteristics of the neonates who composed the study population. The mean cumulative dosage of hydrocortisone treatment was 5.3 ± 1.4 mg (median: 6 mg; range: 2–6 mg). Four preterm infants received a second hydrocortisone course. As for cardiovascular support in addition to dopamine administration, only 1 preterm and 1 term neonate received dobutamine for 24 and 48 hours, respectively. Epinephrine was not used in the neonates who were enrolled in this study. Finally, all but 1 neonate were started on hydrocortisone on postnatal day 5 or later. The preterm infant who was started on hydrocortisone on the first postnatal day had a closed ductus arteriosus before the initiation of hydrocortisone treatment and therefore likely was beyond the period of acute postnatal hemodynamic adaptation.


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  		TABLE 1 Clinical Data

 
The changes in cardiovascular function, systemic hemodynamics, and organ blood flow in the preterm infants are shown in Table 2 and Figs 1 and 2. In the 15 preterm infants studied, BP increased (P < .001, ANOVA) and dopamine requirements decreased (P < .001, ANOVA) after hydrocortisone administration (Table 2, Fig 1). However, although BP increased by 18% within 2 hours after the first dose of hydrocortisone, the increase in BP reached statistical significance only at 6 to 12 hours by pairwise comparisons to the baseline (P < .02; Fig 1A). By the end of the first 12 hours of hydrocortisone treatment, the 28% increase in the BP (P < .02) paralleled that in the SVR (P < .03; Fig 1C) without changes in stroke volume or left ventricular output (Fig 1 E and G). During this period, dopamine dosage significantly decreased (P < .001; Fig 1B). By 24 hours, the dosage of dopamine continued to decrease (P < .001), whereas stroke volume increased (P < .02) without additional changes in the SVR. At the end of the 48 hours of hydrocortisone treatment, the dosage of dopamine decreased by 72% (P < .001); BP and stroke volume increased by 31% (P < .01) and 33% (P < .03), respectively; and SVR tended to increase (14%; P > .05) compared with the baseline. Although heart rate decreased (P < .001; Fig 1F), the increase in stroke volume (P < .03) resulted in a trend for the left ventricular output also to increase (21%; P > .05) by the end of the study. Load-independent contractility, as assessed by the VCFc-WS relation, did not change and remained within 1 SD of normative values throughout the study (Fig 1H). Similarly, there was no change in load-dependent measures of myocardial contractility during the study as assessed by the changes in SF or VCFC (P = .14 and P = .25, respectively). Finally, global myocardial function (MPI) also remained unchanged during the 48 hours of hydrocortisone administration (P = .22; Table 2). Figure 2 depicts the individual and mean changes in mean BP, SVR, and left ventricular output in the 15 preterm infants.


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  		TABLE 2 Hemodynamic Data in Preterm Neonates (n = 15)

 

Figure 1
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  		FIGURE 1 Changes in preterm neonates (n = 15) in mean BP (A; a P < .02, b P < .03, c P < .01) and dopamine dosage (DA) (B; a P < .001) and percentage changes relative to baseline (0 hour) in SVR (C; a P < .03), WS (D), stroke volume (SV) (E; a P < .02, b P < .03), heart rate (HR) (F; a P < .01, b P < .001), and left ventricular output (LVO) (G) are shown at 1, 2, 6 to 12, 24, and 48 hours after the first dose of hydrocortisone. In addition, H depicts the changes in load-independent contractility as assessed by the VCFc-WS relation. HC with arrows indicate approximate timing of hydrocortisone doses. Significant P values for pairwise comparisons versus the baseline (0 hour) with adjustment for multiple comparisons (Bonferroni) are shown. See text for details.

 

Figure 2
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  		FIGURE 2 Absolute individual (gray) and mean (black) changes in BP (A) and the relative individual (gray) and mean (black) changes in SVR (B) and LVO (C) in preterm neonates (n = 15). a Statistical significance. See text for detail.

 
Analysis of the findings in the 5 term infants showed a similar pattern of changes in systemic hemodynamics to those seen in the preterm neonates (Table 3 and Figs 3 and 4). However, except for the decrease in dopamine requirement by 48 hours, the changes did not reach statistical significance. The lack of the similarity in the statistical findings between the preterm and term neonates likely is attributable to the small number of term neonates enrolled. Finally, as in the preterm neonates, the pattern of the changes in mean BP, SVR, and left ventricular output does not reveal significant unexpected individual variability among the term infants (Fig 4).


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  		TABLE 3 Hemodynamic Data in Term Neonates (n = 5)

 

Figure 3
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  		FIGURE 3 Changes in term neonates (n = 5) in mean BP (A) and DA (B; a P < .001) and percentage changes relative to baseline (0 hour) in SVR (C), WS (D), SV (E), HR (F), and LVO (G) are shown at 1, 2, 6 to 12, 24, and 48 hours after the first dose of hydrocortisone. H depicts the changes in load-independent contractility assessed by the VCFc-WS relation. HC with arrows indicate approximate timing of hydrocortisone doses. Significant P value for pairwise comparisons versus the baseline (0 hour) with adjustment for multiple comparisons (Bonferroni) is shown. See text for details.

 

Figure 4
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  		FIGURE 4 Absolute individual (gray) and mean (black) changes in BP (A) and the relative individual (gray) and mean (black) changes in SVR (B) and LVO (C) in term neonates (n = 5). See text for details.

 
For the entire group (n = 20), the change in urine output during the 6 hours before and after the first dose of hydrocortisone was not significant (3.8 ± 2.6 mL/kg per hour vs 4.9 ± 3.1 mL/kg per hour; P = .3). Fluid balance during the 12 hours before and after the first hydrocortisone dose also remained unchanged (51 ± 49 mL/kg vs 43 ± 63 mL/kg; P = .66). Similarly, there was no significant difference in the base excess before hydrocortisone and 24 hours after the first dose of hydrocortisone (–1.9 ± 3.8 mEq/L vs –0.5 ± 3.1 mEq/L; P = .2).

As for the organ blood flow assessments in the MCA and right renal artery in the preterm neonates, there was no change in the PI, MV, or VTI in either vessel (Table 2). Correction for the effects of CO2 and hematocrit on CBF by analysis of covariance did not affect the findings in the MCA. Although the VTI in the MCA tended to increase (P = .066), the concurrent changes in heart rate make the VTI findings clinically irrelevant. Finally, the pattern of changes in PI, MV, and VTI in the MCA and right renal artery were similar in term infants to those seen in the preterm neonates (Table 3).


   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
CONCLUSIONS
 REFERENCES
 
Recent studies have demonstrated an increase in BP and urine output and a decrease in vasopressor requirement after corticosteroid administration in preterm and term neonates with vasopressor-resistant hypotension.13,17,18,24–27 Although these observations suggest an improvement in systemic blood flow, no previous study has investigated systematically the changes in systemic hemodynamics after corticosteroid treatment. The findings of the present study demonstrate that, in preterm and term neonates who require high-dosage vasopressor support to maintain BP in the minimally acceptable range beyond the period of immediate postnatal transition, low-dosage hydrocortisone administration is associated with an improvement in BP and stroke volume, an increase in SVR, and a decrease in the heart rate and the need for vasopressor support. In addition, there was a trend toward an increase in cardiac output after the initiation of hydrocortisone treatment. These hydrocortisone administration–associated cardiovascular changes were not accompanied by alterations in myocardial function or CBF and renal blood flow in our nonhypotensive patients with vasopressor resistance.

That the neonates in this study maintained their BP in the minimally acceptable range on high-dosage vasopressor support is an important hemodynamic feature of this patient population and indicates that these patients were not in uncompensated shock when hydrocortisone treatment was initiated. Therefore, the finding that the hydrocortisone administration–associated cardiovascular changes were not accompanied by changes in CBF and renal blood flow can be explained by the presence of adequate systemic perfusion and probably intact CBF autoregulation on high-dosage dopamine before hydrocortisone treatment was initiated. In addition, it is important to emphasize that our findings relate to preterm and term neonates beyond the period of immediate postnatal hemodynamic transition and that they may not apply to the <1-day-old very preterm infant during the immediate postnatal transitional period with significant shunting across the fetal channels.

We previously reported an improvement in BP by 2 hours and a decreased need for vasopressor support by 6 to 12 hours after the initiation of corticosteroid administration in preterm neonates with vasopressor-resistant hypotension.17,24 These temporal relations were similar in the present study as there was an 18% increase in the BP within 2 hours of hydrocortisone administration (Table 2 and Fig 1A). However, in this study, the rise in BP reached statistical significance by 6 to 12 hours only for preterm infants.

The exact mechanisms by which hydrocortisone administration leads to an increase in BP in neonates with vasopressor resistance are not known. However, genomic upregulation of the expression of cardiovascular adrenergic and angiotensin type 2 receptors and their second messenger systems and the inhibition of the expression of inducible nitric oxide synthase and vasodilatory prostaglandin action are thought to contribute to the cardiovascular effects of hydrocortisone in neonates with vasopressor resistance.17,29,30 In addition, certain nongenomic effects such as the inhibition of catecholamine metabolism and the increase in intracellular calcium availability and capillary integrity may be responsible, at least in part, for the relatively rapid onset of the hydrocortisone-induced improvement in BP.29,30 In other words, corticosteroids increase the sensitivity of the cardiovascular system to endogenous or exogenous catecholamines, resulting in improvements in myocardial contractility and increases in SVR and effective circulating blood volume. In addition, at least in the critically ill preterm and term neonate with relative adrenal insufficiency, low-dosage hydrocortisone administration also serves as hormone replacement therapy.23

Because BP is the product of the interaction between cardiac output and SVR, the hydrocortisone administration–associated increase in BP can be the result of an increase in cardiac output, SVR, or both. In our study, the initial rise in BP paralleled that in the SVR; at 24 and 48 hours, the improvement in BP resulted more from an increase in stroke volume, whereas SVR tended to decrease. Of note is that at 24 to 48 hours, SVR still tended to be higher than before the start of hydrocortisone treatment despite the significant decrease in the dosage of dopamine. Because the neonatal myocardium is especially sensitive to the increase in afterload,28 the findings that cardiac output was not compromised and that contractility remained normal and unchanged even while SVR increased significantly during the first 6 to 12 hours are of importance and clinically reassuring.

In the clinical practice, dobutamine frequently is added to dopamine once dopamine requirement reaches 15 to 20 µg/kg per minute. The rationale for this practice is to provide a more effective inotropic support in the face of the suspected increase in the SVR caused by dopamine's vasopressor activity. In addition, dobutamine may be added and the dosage of dopamine decreased to remedy the anticipated myocardial dysfunction that is present in some neonates with hypotension.39 In our patients with vasopressor resistance that presents after the immediate postnatal hemodynamic transition, myocardial contractility was normal even before the start of hydrocortisone treatment and remained unchanged despite the increase in SVR. Therefore, the rationale for the addition of dobutamine to dopamine in this clinical setting seems unwarranted unless evidence for myocardial dysfunction can be found. In our study, 2 neonates received dobutamine in addition to dopamine. Dobutamine treatment was initiated on the basis of clinical impression rather than echocardiographic evidence of myocardial dysfunction and was weaned off within 24 to 48 hours. It is interesting that even in patients with normal myocardial function, dobutamine may increase BP through augmentation of the cardiac output to supranormal levels.40 Whether driving the myocardium to a hyperdynamic contractile state results in untoward short- and/or long-term cardiac effects remains unknown.

Although VTI tended to increase in the MCA in preterm infants, PI and MV did not change. Because heart rate significantly decreased during the study and because VTI is affected independently by the heart rate, the PI and the MV rather than the VTI are the indices that are reflective more accurately of the changes in organ blood flows in our patients. Therefore, as noted earlier, the absence of significant changes in PI and MV and that urine output and base excess were adequate and remained unchanged suggest that our patients, despite receiving dopamine at doses ≥15 µg/kg per minute, had been maintaining adequate organ blood flow even before the initiation of hydrocortisone treatment. However, because of the small sample size, firm conclusions on the potential independent effects of hydrocortisone on organ blood flow cannot be drawn.

Contrary to our previous studies,17,24 the increase in urine output after hydrocortisone treatment did not reach statistical significance. Again, this discrepancy may be explained by the fact that the patients in the present study were started on low-dosage hydrocortisone before having developed the uncompensated phase of shock characterized by hypotension and poor vital organ perfusion. Therefore, a severe disturbance of renal perfusion and function was unlikely to have been present when hydrocortisone was started. Of note is that it would have been very difficult to design and carry out a study that involved neonates with fully evolved vasopressor-resistant hypotension because the time required to complete the functional echocardiography studies could have led to unacceptable delays in the initiation of hydrocortisone treatment.

The limitations of the study are its nonrandomized nature and the small sample size. The impact of these limitations is lessened by the serial measurements of cardiovascular parameters with each patient serving as his or her own control. The limitations of the ultrasonographic methods that are available for bedside assessment of organ blood flow also are of importance because they detect only relative changes in blood flow and in a noncontinuous manner. In addition, although the changes in the PI, MV, and VTI have been shown to correlate with invasive measures of organ blood flow,36–38 these indices rely on detecting changes in blood velocity with the assumption that vessel diameter remains constant. Finally, as mentioned above, because of the logistics of the hemodynamic measurements, neonates who were enrolled in this study had minimally acceptable BPs on high-dosage vasopressor support and were not in full-blown uncompensated shock.

In the absence of long-term follow-up data, the effect of hydrocortisone and/or the drug-induced hemodynamic improvement on the neurodevelopmental outcome of preterm and term neonates remains unknown. Although, contrary to dexamethasone, hydrocortisone may have no effect on long-term neurodevelopment when administered after the first postnatal week,41 no study has investigated the potential untoward neurodevelopmental effects of early hydrocortisone administration in preterm neonates.30


   CONCLUSIONS
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
REFERENCES
 
The findings of the present study demonstrate that low-dosage hydrocortisone that is administered to preterm and term neonates with minimally acceptable BPs while on high-dosage dopamine infusion improves BP without compromising myocardial function and organ blood flow and decreases the need for vasopressor support.


   FOOTNOTES
 
Accepted Jun 1, 2006.

Address correspondence to Shahab Noori, MD, USC Division of Neonatal Medicine, Childrens Hospital Los Angeles, 4650 Sunset Blvd, MS #31, Los Angeles, CA 90027. E-mail: snoori{at}chla.usc.edu

The authors have indicated they have no financial relationships relevant to this article to disclose.

This work was presented in part at the annual meeting of Pediatric Academic Societies; May 14-17, 2005; Washington, DC.


   REFERENCES
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 METHODS
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 DISCUSSION
 CONCLUSIONS
 REFERENCES
 

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PEDIATRICS (ISSN 1098-4275). ©2006 by the American Academy of Pediatrics




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