ATS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ando, M.
Right arrow Articles by Takahashi, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ando, M.
Right arrow Articles by Takahashi, Y.
Related Collections
Right arrow Congenital - cyanotic

Ann Thorac Surg 2005;80:1672-1678
© 2005 The Society of Thoracic Surgeons

Original article: Cardiovascular

Steroid Supplementation: A Legitimate Pharmacotherapy After Neonatal Open Heart Surgery

Makoto Ando, MD * , In-Sam Park, MD, Naoki Wada, MD, Yukihiro Takahashi, MD

Department of Pediatric Cardiac Surgery, Sakakibara Heart Institute, Tokyo, Japan

Accepted for publication April 25, 2005.

* Address correspondence to Dr Ando, Department of Pediatric Cardiac Surgery, Sakakibara Heart Institute, 3-16-1 Asahi-cho, Fuchu-si, Tokyo, 183-0003 Japan (Email: maando{at}shi.heart.or.jp).

Presented at the Forty-first Annual Meeting of The Society of Thoracic Surgeons, Tampa, FL, Jan 24–26, 2005.


   Abstract
Top
 Abstract
Introduction
 Patients and Methods
 Results
 Comment
 Discussion
 References
 
BACKGROUND: An inflammatory response together with multiple organ failure subsequent to cardiopulmonary bypass is especially prominent in neonates. The behavior of glucocorticoids during this period in these patients is not known. If adrenal insufficiency should exist, it could considerably compromise postoperative recovery.

METHODS: Twenty neonates undergoing biventricular repair were enrolled. Ten patients were assigned to receive hydrocortisone treatment and the other 10 to receive placebo. The treatment group received stress-dose hydrocortisone sodium succinate after discontinuation of cardiopulmonary bypass: 0.18 mg·kg–1 ·hr–1 for 3 days, 0.09 mg·kg–1 ·hr–1 for 2 days, and 0.045 mg·kg–1 ·hr–1 for 2 days. The placebo was 5% glucose solution.

RESULTS: Patients had adrenal insufficiency (cortisol < 5 µg/dL) from 24 to 72 hours in the placebo group. This was associated with a simultaneous reduction of left ventricular shortening fraction (p < 0.0001, analysis of variance; p = 0.0203, Student's t test), the necessity to increase inotropic agents (p = 0.043, analysis of variance), and an increase in serum lactate level (p = 0.049, Student's t test). During this period, serum cortisol level was maintained above the normal level (>23 µg/dL) in the hydrocortisone group. The placebo group had a greater positive fluid balance (p = 0.027, Student's t test) and greater total body edema in the immediate postoperative period (p = 0.065, Student's t test). Blood oxygenation constantly improved, and the duration on mechanical ventilation was shorter (83.5 ± 42.1 versus 138.2 ± 89.7 hours; p = 0.098) in the hydrocortisone group.

CONCLUSIONS: Adrenal insufficiency may occur after neonatal open heart surgery. Stress-dose hydrocortisone supplementation blunts other organ dysfunction and can be considered a legitimate pharmacotherapy in this cohort.


   Introduction
Top
 Abstract
 Introduction
Patients and Methods
 Results
 Comment
 Discussion
 References
 
It is well known that an inflammatory response together with multiple organ failure occurs subsequent to cardiopulmonary bypass, especially in young children [1]. This is most prominent at 8 to 24 hours after cardiopulmonary bypass [2, 3].

The behavior of glucocorticoids, whose function is to maintain stress-related homeostasis, during this period is not known. Immature neonates may have an inappropriate adrenal response to stress. If adrenal insufficiency should exist, it could considerably compromise postoperative recovery.

This study was designed to (1) test the hypothesis that adrenal insufficiency exists after cardiopulmonary bypass in neonates and (2) assess the legitimacy of the routine use of steroid administration for this patient cohort.


   Patients and Methods
Top
 Abstract
 Introduction
 Patients and Methods
Results
 Comment
 Discussion
 References
 
Twenty neonates (within 28 days after birth) undergoing complete biventricular repair were enrolled. The exclusion criteria were mechanical ventilation, evidence of infection, receiving more than renal dose dopamine (>5 µg·kg–1 ·min–1), and genetic disorder or chromosomal abnormality. The protocol was approved by our institutional review board, and informed consent was obtained from all parents. The study was conducted from February 2002 to June 2004.

Ten patients were assigned to receive hydrocortisone treatment and the other 10 to receive placebo. The blinded generator (a pharmacist) manipulated the patient assignment so that interanatomic variations were matched between the two groups. The treatment group received hydrocortisone sodium succinate after discontinuation of cardiopulmonary bypass: 0.18 mg·kg–1 ·hr–1 for 3 days, 0.09 mg·kg–1 ·hr–1 for 2 days, and 0.045 mg·kg–1 ·hr–1 for 2 days. The placebo was 5% glucose solution. The allocation was concealed to all clinical participants and the data interpreter.

Anesthetic management included fentanyl-sevoflurane anesthesia with neuromuscular blockade achieved by periodic vecuronium infusion. Methylprednisolone sodium succinate, 30 mg/kg, was given during induction of anesthesia. Operation was performed through a median sternotomy. A roller pump was used, and the rate adjusted to 2.5 L·m–2 ·min–1. Pump prime consisted of crystalloid solution, 20% mannitol, sodium bicarbonate, 25% albumin, and packed red blood cells. Continuous ultrafiltration was performed throughout cardiopulmonary bypass using a dialysis filter (APF-01D; Asahi Medical, Tokyo, Japan) circuit connected to the arteriovenous circuit. Blood cardioplegic solution was given every 20 minutes at a dose of 20 mL/kg. Hypothermic myocardial protection was achieved by core cooling to bladder temperature of 28°C. Hematocrit was maintained at greater than 30%. In a case with coarctation or interruption of the aorta, systemic perfusion was achieved through a polytetrafluoroethylene tube anastomosed to the right innominate artery. Perfusion to the brain was maintained at 30 mL·kg–1 ·min–1 while end-to-side arch anastomosis was performed. Circulatory arrest was not used. Patients were weaned from cardiopulmonary bypass after the bladder temperature reached 35°C and circulating blood was concentrated to a hematocrit of 40%. A Quinton peritoneal dialysis catheter (Kendall, Mansfield, MA) was inserted in all patients. Baseline characteristics of the patients are summarized in Table 1.


View this table:
[in this window]
[in a new window]
  		Table 1. Baseline Characteristics With p Values by Univariate Analyses
 
Postoperative data collection started when the patient returned to the intensive care unit. Dopamine was routinely administered at a dose of 5 µg·kg–1 ·min–1. Second-line inotropic agents included epinephrine when the blood pressure was low and milrinone when the blood pressure was high. The use of neuromuscular blockade, diuretics, and peritoneal dialysis was decided by the bedside physician. Typically, diuretics (furosemide, 1 to 4 mg·kg–1 ·day–1) were begun on the first postoperative morning.

The radiologic soft tissue index was calculated as the ratio of the dimension of soft tissues measured at the height of the eighth rib to the diameter of the eighth rib measured at the midclavicular line [4]. The alveolar–arterial oxygen difference was calculated as the fraction of inspired oxygen times the difference between the barometric pressure (760 mm Hg) and water vapor pressure (47 mm Hg) minus the arterial partial pressure of carbon dioxide divided by the respiratory quotient (0.8), minus the arterial partial pressure of oxygen. Blood samples were transferred to a sterile vacuum flask containing ethylenediaminetetraacetic acid, and immediately centrifuged. The separated plasma was kept in a refrigerator until measurement. Serum cortisol, adrenocorticotropic hormone, and interleukin 6 levels were measured using radioimmunoassay, immunoradiometric assay, and chemiluminescent enzyme immunoassay, respectively. Left ventricular shortening fraction was the ratio of end-systolic to end-diastolic left ventricular dimensions on a two-dimensional echocardiogram using an SSD-550 system (ALOKA Inc, Tokyo, Japan). Measurements were performed exclusively by one cardiologist. Inotrope score was calculated as dopamine (x1) + epinephrine (x100) + milrinone (x15) [5]. Complete blood cell count, liver and renal profiles, serum electrolyte levels, and blood glucose level were determined before discharge to assess the presence of rebound adrenal insufficiency in the hydrocortisone group.

SPSS statistical software for Windows (version 11.0; SPSS Inc, Chicago, IL) was used for data analysis. Values were expressed as mean ± standard deviation. Differences between groups were examined by Student's t test (continuous variables) or Pearson's {chi}2 test (categorical variables). Two-way repeated-measures analysis of variance was used to assess overall group differences for data with repeated measurements over time. All probability values were two-tailed.


   Results
Top
 Abstract
 Introduction
 Patients and Methods
 Results
Comment
 Discussion
 References
 
Postoperative Course
There was no mortality. Left phrenic nerve palsy was observed in 1 patient in the hydrocortisone group. This patient required subsequent diaphragmatic plication. One patient in the placebo group had pneumonia caused by Serratia organisms, which required prolonged treatment with antibiotics. In these patients, symptoms were detected after the patient was weaned from the ventilator. Significant postoperative morbidity was not seen in the rest of the patients. Representative postoperative data are listed in Table 2. Stay in the intensive care unit and in the hospital in the placebo group was 13.4 ± 6.5 and 24.6 ± 11.9 days, versus 10.2 ± 3.0 and 24.2 ± 8.6 days in the hydrocortisone group. These differences were not significant.


View this table:
[in this window]
[in a new window]
  		Table 2. Representative Data Measured After Operation a
 
Serum Cortisol and Adrenocorticotropic Levels
In the placebo group, serum cortisol level was less than 5 µg/dL from 24 to 72 hours (2.8 ± 3.3 µg/dL at 24 hours, 2.8 ± 3.9 µg/dL at 48 hours, and 4.6 ± 4.3 µg/dL at 72 hours; Fig 1). It gradually increased to a low-normal level (10.4 ± 3.8 µg/dL) on day 7. On the other hand, cortisol level in the hydrocortisone group was 43.6 ± 8.4 µg/dL at 12 hours. The value gradually decreased thereafter, but was maintained above the normal range (4 to 23 µg/dL) until 72 hours (23.3 ± 7.2 µg/dL). On the other hand, there was no significant difference in the adrenocorticotropic level between the two groups. It was maintained in the low-normal range from 0 to 72 hours after operation.



View larger version (20K):
[in this window]
[in a new window]
  		Fig 1. Serum cortisol level (A) and adrenocorticotropic hormone (ACTH) level (B) are shown for placebo (dashed line) and hydrocortisone (solid line) groups. The normal range for both is indicated as a bar on the right side. Data are expressed as mean ± standard deviation. For cortisol level, ***p < 0.01, **p < 0.05 by Student's t test. The p values for effects of time, group (cortisol versus placebo), and their interaction in analysis of variance were all <0.0001. There was no significant difference between groups for serum adrenocorticotropic hormone level by both Student's t test and analysis of variance.

 
Hemodynamic Profile and Respiratory Function
In the hydrocortisone group, left ventricular shortening fraction continuously increased and inotrope score continuously decreased with time (Fig 2). In the placebo group, left ventricular shortening fraction decreased temporarily from 6 to 12 hours with an increased inotrope score from 18 to 24 hours. During this time, there was no significant difference in mean arterial blood pressure between the two groups. In the hydrocortisone group, serum lactate level continuously decreased after 6 hours. On the other hand, lactate decreased temporarily, but stayed at the same level from 12 to 24 hours in the placebo group. The total duration of inotropic agent infusion after operation was 188.5 ± 82.1 hours in the placebo group and 135.4 ± 47.1 hours in the hydrocortisone group (p = 0.093). The total duration of mechanical ventilation after operation was 138.2 ± 89.7 hours in the placebo group and 83.5 ± 42.1 hours in the hydrocortisone group (p = 0.098), despite the fact that the alveolar–arterial oxygen difference was greater in the hydrocortisone group at 3 hours.



View larger version (23K):
[in this window]
[in a new window]
  		Fig 2. Inotrope score (A), left ventricular (LV) shortening fraction on echocardiogram (B), and serum lactate level (C) are shown for placebo (dashed line) and hydrocortisone (solid line) groups. Data are expressed as mean ± standard deviation. **p < 0.5, *p < 0.1 by Student's t test. The p values for effects of time, group, and their interaction in analysis of variance were <0.0001, 0.68, and 0.043 for inotrope score, <0.0001, 0.219, and 0.0001 for shortening fraction, and <0.0001, 0.59, and 0.187 for serum lactate level.

 
Net Fluid Balance and Generalized Edema
In the hydrocortisone group, urine output was maximal on the third day, whereas maximal urine output was observed on the sixth day in the placebo group (Fig 3). Peritoneal dialysis was used in 6 patients in the placebo group and 1 patient in the hydrocortisone group (p = 0.019). Net fluid balance was negative on the second and third days in the hydrocortisone group, whereas the balance was positive until the fourth day in the placebo group. Radiologic soft tissue index was higher in the placebo group throughout the immediate postoperative period.



View larger version (25K):
[in this window]
[in a new window]
  		Fig 3. Urine output (A), net fluid balance (B), and radiologic soft tissue index (C) are shown for placebo (black bars) and hydrocortisone (white bars) groups. **p < 0.5, *p < 0.1 by Student's t test. Data are expressed as mean ± standard deviation. (Op = amount during operation.)

 
Circulating Cytokines
Interleukin 6 level (pg/mL) in the placebo and hydrocortisone groups was 39.5 ± 39.1 versus 19.4 ± 12.4 at 0 hours (p = 0.173), 98.5 ± 30.5 versus 86.2 ± 43.8 at 12 hours (p = 0.566), and 120.5 ± 96.7 versus 99.4 ± 83.2 at 24 hours (p = 0.661), respectively. C-reactive protein tended to be higher in the placebo group on the third day (2.2 ± 2.1 versus 1.3 ± 0.9 mg/dL), but the difference was not significant (p = 0.27).

Laboratory Data Before Discharge
Data were obtained at 20.7 ± 9.5 days in the placebo group and at 19.4 ± 8.5 days in the hydrocortisone group. There was no significant difference in the white blood cell differential counts, liver and renal profiles, serum electrolyte levels, and glucose levels (Table 3).


View this table:
[in this window]
[in a new window]
  		Table 3. White Blood Cell Counts and Serologic Data Before Discharge
 

   Comment
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
Discussion
 References
 
Inflammation after cardiopulmonary bypass has been linked to multiple organ failure involving the myocardium, lung, kidney, pancreas, and central nervous system [6]. Especially, neonates are more susceptible to systemic inflammation compared with older infants and children [7]. Kristof and Magder [2] suggested that the inflammatory response may be maximal at 8 hours after cardiopulmonary bypass in adult patients. Wernovsky and associates [3] reported that a decrease in cardiac index occurs during the night after arterial switch operation in neonates and infants.

The behavior of glucocorticoids produced by the immature adrenal gland of the neonatal patient, which should function as the peripheral limb of the stress system, is not known. This study showed that adrenal insufficiency may occur in neonates undergoing open heart surgery. This was seen from 12 hours up to the third day in our cohort. This was associated with a decrease in myocardial contractility, a necessity to increase inotropic agents, and an increase in serum lactate level. Supplementation of hydrocortisone blunted these phenomena. The dose of hydrocortisone used in this study provides a quantity of cortisol equal to the maximal daily rate of secretion in response to stress [8]. It has been demonstrated that its use reduces the duration of vasopressor support in sepsis patients [9], and also attenuates systemic inflammation in adult patients after cardiac surgery [10]. The placebo group had a greater positive fluid balance and greater total body edema in the immediate postoperative period. Blood oxygenation constantly improved, and the duration on mechanical ventilation was shorter in the hydrocortisone group. Steroid administration during cardiopulmonary bypass improves arterial oxygenation in congenital heart surgery [11]. Previous studies have chiefly compared placebo and steroid administration during or preceding cardiopulmonary bypass [12], and few studies have addressed the effectiveness of glucocorticoids in postoperative patients with congenital heart disease [5].

Recently, bolus steroid administration before cardiopulmonary bypass has become common practice [11]. It is known that the use of corticosteroids for several days or up to a few weeks does not lead to adrenal insufficiency [13]. However, the immature pituitary–adrenal axis in neonates may respond differently. Suppression of the pituitary–adrenal axis by a preoperative bolus of methylprednisolone may be one reason for the low cortisol levels observed after operation. However, the adrenocorticotropic level, which was maintained within the normal range, suggests that this is not the sole reason. Another potential reason is the ultrafiltration used during cardiopulmonary bypass, which may remove glucocorticoids from the circulation. Because the cortisol level at 0 hour was maintained within the normal range, this cannot be considered a major reason either. It is known that adrenal insufficiency may present in severely ill patients such as those with septic shock [14]. The third potential reason is, therefore, that the pituitary–adrenal axis may be affected as a part of systemic inflammation or organ dysfunction. In this context, it may aggravate other organ dysfunction present simultaneously.

It has been increasingly recognized that circulating cytokines are involved in postbypass inflammation and organ dysfunction [15]. Tumor necrosis factor-{alpha} and interleukin 1ß were shown to depress myocardial function [16, 17]. The level of interleukin 6 was measured in this study because it is demonstrated to be most predictive of hemodynamic disorder after cardiac surgery [18]. Glucocorticoids suppress the production of interleukin 6 and other proinflammatory cytokines such as interleukin 1ß by decreasing the transcription rates of the genes and the stability of the messenger RNA [19–21]. The present study failed to demonstrate a role of interleukin 6 in the measurable improvement by hydrocortisone supplementation. Interleukin 6 reaches the maximal point immediately after cardiopulmonary bypass and increases again from 12 to 24 hours in adult patients [18]. This change, triggered by cardiopulmonary bypass, may not be altered by postbypass steroid supplementation. Moreover, the pattern of this alteration may be different in pediatric patients [15]. Therefore, the measurement points selected in this study might not reflect the maximal values.

The side effects of glucocorticoids include peptic ulcer disease, increased risk of infection, and suppression of the pituitary–adrenal axis [13]. These trends were not seen in the hydrocortisone group. It is recognized that the increased risk of infection, as observed in high-dose glucocorticoid studies, is not seen with low-dose infusion [9, 10]. Laboratory studies before discharge from the hospital showed no evidence of rebound adrenal insufficiency in the hydrocortisone group. Moreover the behavior of adrenocorticotropic hormone, which did not show any difference between the two groups, indicates that pituitary suppression caused by infusion of a stress-dose hydrocortisone was minimal.

The limitations of this study are as follows: (1) The low statistical power of the study was caused by the small sample size. (2) Three different anatomic variations were included to increase the power of the study. This may have made the cohort heterogeneous and could confound the analysis. (3) Shortening fraction is a measure that is subject to bias of the interpreter. Moreover, the load-dependent nature of the data [22] may have interfered with precise measurement of contractility. Because there was no difference in mean arterial pressure between the two groups, the influence of afterload may be minimal, but is still a potential concern. (4) Normal values of cortisol in adults may not apply to neonates. Values less than 5 µg/dL may not be evidence of distinct adrenal insufficiency in neonates. (5) The alterations of values of cortisol observed in this study may not be capable of being generalized to other management strategies because they may be influenced by multiple perioperative management strategies including compound, dose, timing of prebypass steroid infusion, and the ultrafiltration method during cardiopulmonary bypass.

Even with these limitations, the results of this study led us to conclude that (1) adrenal insufficiency may occur after neonatal open heart surgery, (2) stress-dose hydrocortisone supplementation blunted other organ dysfunction in this patient cohort, (3) this treatment did not increase the risk of infection, peptic ulcer disease, or pituitary–adrenal suppression, (4) and, therefore, this treatment can be considered a legitimate pharmacotherapy after neonatal open heart surgery.


   Discussion
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 Discussion
References
 
DR PETER B. MANNING (Cincinnati, OH): The generalized inflammatory response to cardiopulmonary bypass and the resultant end-organ dysfunction, especially cardiac and pulmonary, has long been a nemesis of cardiac surgeons, particularly those who care for newborns, a population that seems particularly sensitive to this phenomenon. Steroids have been employed longer than any modality to counteract this process because of their long recognized potent yet nonspecific antiinflammatory effects.

Recent work, including data from our institution, has demonstrated that preoperative steroid dosing given 4 hours before surgery can more effectively attenuate the inflammatory response compared with intraoperative dosing alone. In the study just presented by Dr Ando, the continuation of steroids through 7 days postoperatively resulted in improved clinical outcome parameters, particularly related to fluid balance and pulmonary function. Although the study is not powered because of small sample size to demonstrate a statistically significant improvement in many of their parameters, the beneficial effects were clear.

I congratulate the authors on being able to establish two comparable and reasonably homogeneous study groups in the newborn age group, but even though these newborns represent an at-risk population, the excluded single ventricle and mechanically ventilated patients likely represent a much larger and still higher risk group in whom the benefit of such therapy may be still greater.

I believe a much more important contribution this study makes is the demonstration of adrenal insufficiency in the placebo group. Defining adrenal insufficiency is problematic in this population because very limited data do exist regarding normal values for cortisol or adrenocorticotropic hormone (ACTH) level. Relative adrenal insufficiency, defined as an inadequate response to the hypothalamic–pituitary–adrenal axis to stress, has been recognized in adult and pediatric populations to be associated with catecholamine-resistant low cardiac output syndrome. In more recent data from our center presented at last week's Society of Critical Care Medicine meeting in Phoenix, we found that infants with congenital heart disease and catecholamine-resistant low cardiac output syndrome and with low baseline cortisol levels whom we routinely treat with exogenous steroids had a markedly improved survival compared with those patients with a higher baseline cortisol level.

However, we defined 15 µg/dL as an inappropriately low baseline cortisol level, whereas Dr Ando and his colleagues used a more stringent level of 5 µg/dL to define adrenal insufficiency. Almost all of the patients in your study, regardless of baseline cortisol level, demonstrated a normal response to Cortrosyn stimulation, suggesting a central rather than peripheral etiology for the relative adrenal insufficiency, a finding that is consistent with the current study's observation of low ACTH levels in the placebo group.

Despite the beneficial effects of postoperative steroid administration demonstrated in this study, the authors have suggested that the relative adrenal insufficiency they observed may in fact be iatrogenic, induced by the routine administration of steroids in the pump prime. Do you believe that steroids are too much of a good thing or not enough of a good thing? What is your current recommendation regarding who should receive exogenous steroids, only specific age groups? Should cortisol levels be used as a guide, and if so, what cortisol level do you consider abnormal in a postoperative newborn? If steroid use is recommended routinely, when should it be given: preoperatively, intraoperatively, postoperatively, or a combination?

I thank Dr Ando for supplying me the manuscript in advance and The Society for the privilege of discussing this paper.

DR ANDO: Thank you very much, Dr Manning, for very nice comments and questions. I would like to respond to your comments first. We selected this patient group because they had a relatively stable postoperative course and data acquisition was more feasible. However, I think it is true that patients who need this kind of treatment most are those with more severe diseases, namely those with a single-ventricle physiology undergoing Norwood or other type of operation, and we more frequently see severe inflammatory response and progressive capillary leak in this patient subset. We also see that stress-dose steroid supplementation is ineffective in the face of very severe inflammation. In this context we have to switch it to more potent steroid treatments such as methylprednisolone bolus or betamethasone.

And responding to some of your questions, obviously stress caused by cardiopulmonary bypass is enormous, and I think it is already demonstrated that the prebypass bolus steroid prophylaxis is effective to reduce adverse outcomes after cardiopulmonary bypass, and I do not have any objection to using these bolus steroids before cardiopulmonary bypass.

Regarding the age group, besides this patient group, we also measured cortisol levels in some older infants and children, and what we found is that depression of cortisol level is possible with older children if they are distressed after operation. So I think it is reasonable to use steroids for these older children, adolescents, or adults if they are distressed after operation.

And as to the recommended cortisol level, I said 5 µg/dL in this slide, but this was the level indicating adrenal insufficiency when observed in the resting state, and in the face of stress like a postbypass situation, I totally agree with Dr Manning that at least 15 µg/dL cortisol level is necessary, or even more, and in fact, the target cortisol level in this study was 25 µg/dL.

Finally, regarding the timing of steroid, we recently started a program to initiate steroid 12 to 24 hours before cardiopulmonary bypass in the hope that it may prepare the patient's physiologic condition for the stress of cardiopulmonary bypass. So I would recommend combined use of preoperative, intraoperative, and postoperative steroid administration. I think, again, bolus steroid use before cardiopulmonary bypass is justified. And for the use after operation we recommend a stress-dose of hydrocortisone because it is more physiologic and safe for continuous use. However, in the face of severe distress, maybe stronger treatment becomes necessary, and a combination should be individualized for each patient.

Thank you.


   References
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 Discussion
 References
 

  1. Seghaye MC, Grabitz RG, Duchateau J, et al. Inflammatory reaction and capillary leak syndrome related to cardiopulmonary bypass in neonates undergoing cardiac operations J Thorac Cardiovasc Surg 1996;112:687-697.[Abstract/Free Full Text]
  2. Kristof AS, Magder S. Low systemic vascular resistance state in patients undergoing cardiopulmonary bypass Crit Care Med 1999;27:1121-1127.[Medline]
  3. Wernovsky G, Wypij D, Jonas RA, et al. Postoperative course and hemodynamic profile after the arterial switch operation in neonates and infants. A comparison of low-flow cardiopulmonary bypass and circulatory arrest Circulation 1995;92:2226-2235.[Abstract/Free Full Text]
  4. Tassani P, Barankay A, Haas F, et al. Cardiac surgery with deep hypothermic circulatory arrest produces less systemic inflammatory response than low-flow cardiopulmonary bypass in newborns J Thorac Cardiovasc Surg 2002;123:648-654.[Abstract/Free Full Text]
  5. Shore S, Nelson DP, Pearl JM, et al. Usefulness of corticosteroid therapy in decreasing epinephrine requirements in critically ill infants with congenital heart disease Am J Cardiol 2001;88:591-594.[Medline]
  6. Kirklin JW, Barratt-Boyes BG. Hypothermia, circulatory arrest, and cardiopulmonary bypassIn: Kirklin JW, Barratt-Boyes BG, editors. Cardiac surgery. 3rd ed.. New York: Churchill Livingstone; 2003. pp. 66-130.
  7. Ashraf SS, Tian Y, Zacharrias S, Cowan D, Martin P, Watterson K. Effects of cardiopulmonary bypass on neonatal and paediatric inflammatory profiles Eur J Cardiothorac Surg 1997;12:862-868.[Abstract]
  8. Thomas JP, el-Shaboury AH. Aldosterone secretion in steroid-treated patients with adrenal suppression Lancet 1971;1:623-625.[Medline]
  9. Briegel J, Forst H, Haller M, et al. Stress doses of hydrocortisone reverse hyperdynamic septic shocka prospective, randomized, double-blind, single-center study. Crit Care Med 1999;27:723-732.[Medline]
  10. Kilger E, Weis F, Briegel J, et al. Stress doses of hydrocortisone reduce severe systemic inflammatory response syndrome and improve early outcome in a risk group of patients after cardiac surgery Crit Care Med 2003;31:1068-1074.[Medline]
  11. Schroeder VA, Pearl JM, Schwartz SM, Shanley TP, Manning PB, Nelson DP. Combined steroid treatment for congenital heart surgery improves oxygen delivery and reduces postbypass inflammatory mediator expression Circulation 2003;107:2823-2828.[Abstract/Free Full Text]
  12. Lodge AJ, Chai PJ, Daggett CW, Ungerleider RM, Jaggers J. Methylprednisolone reduces the inflammatory response to cardiopulmonary bypass in neonatal pigletstiming of dose is important. J Thorac Cardiovasc Surg 1999;117:515-522.[Abstract/Free Full Text]
  13. Haynes RC. Adrenocorticotropic hormone; adrenocortical steroids and their synthetic analogs; inhibitors of the synthesis and actions of adrenocortical hormonesIn: Goodman LS, Gilman A, Rall TW, Nies AS, Taylor P, editors. The pharmacological basis of therapeutics. New York: Pergamon Press; 1990. pp. 1431-1462.
  14. Marik PE, Zaloga GP. Adrenal insufficiency during septic shock Crit Care Med 2003;31:141-145.[Medline]
  15. Carvalho MV, Maluf MA, Catani R, et al. Cytokines and pediatric open heart surgery with cardiopulmonary bypass Cardiol Young 2001;11:36-43.[Medline]
  16. Kumar A, Kosuri R, Kndula P, Dimou C, Allen J, Parrillo JE. Effects of epinephrine and amrinone on contractility and cyclic adenosine monophosphate generation of tumor necrosis factor {alpha}-exposed cardiac myocytes Crit Care Med 1999;27:286-292.[Medline]
  17. Cain BS, Meldrum DR, Dinarello CA, et al. Tumor necrosis factor-alpha and interleukin-1beta synergistically depress human myocardial function Crit Care Med 1999;27:1309-1318.[Medline]
  18. Hennein HA, Ebba H, Rodriguez JL, et al. Relationship of the proinflammatory cytokines to myocardial ischemia and dysfunction after uncomplicated coronary revascularization J Thorac Cardiovasc Surg 1994;108:626-635.[Abstract/Free Full Text]
  19. Lee SW, Tsou AP, Chan H, et al. Glucocorticoids selectively inhibit the transcription of the interleukin 1 beta gene and decrease the stability of interleukin 1 beta mRNA Proc Natl Acad Sci USA 1988;85:1204-1208.[Abstract/Free Full Text]
  20. Zanker B, Walz G, Wieder KJ, Strom TB. Evidence that glucocorticosteroids block expression of the human interleukin-6 gene by accessory cells Transplantation 1990;49:183-185.[Medline]
  21. Zitnik RJ, Whiting NL, Elias JA. Glucocorticoid inhibition of interleukin-1-induced interleukin-6 production by human lung fibroblastsevidence for transcriptional and post-transcriptional regulatory mechanisms. Am J Respir Cell Mol Biol 1994;10:643-650.[Abstract]
  22. Colan SD. Noninvasive assessment of myocardial mechanics-a review of analysis of stress-shortening and stress-velocity Cardiol Young 1992;2:1-13.



This article has been cited by other articles:


Home page
 Ann. Thorac. Surg.Home page
O. J. Liakopoulos, J. D. Schmitto, S. Kazmaier, A. Brauer, M. Quintel, F. A. Schoendube, and H. Dorge
Cardiopulmonary and Systemic Effects of Methylprednisolone in Patients Undergoing Cardiac Surgery
Ann. Thorac. Surg., July 1, 2007; 84(1): 110 - 119.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ando, M.
Right arrow Articles by Takahashi, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ando, M.
Right arrow Articles by Takahashi, Y.
Related Collections
Right arrow Congenital - cyanotic

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
ANN THORAC SURG ASIAN CARDIOVASC THORAC ANN EUR J CARDIOTHORAC SURG
J THORAC CARDIOVASC SURG ICVTS ALL CTSNet JOURNALS