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J Thorac Cardiovasc Surg 2008;136:1229-1236
© 2008 The American Association for Thoracic Surgery

Surgery for Congenital Heart Disease

Perioperative course in 118 infants and children undergoing coarctation repair via a thoracotomy: A prospective, multicenter experience

^a Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
^b Los Angeles Children's Hospital, Los Angeles, California
^c Children's Memorial Hospital, Chicago, Illinois
^d Children's Hospital of Wisconsin, Milwaukee, Wisconsin
^e Cleveland Clinic Foundation, Cleveland, Ohio

Received for publication November 27, 2007; revisions received May 7, 2008; accepted for publication June 15, 2008.

^_* Address for reprints: Sarah Tabbutt, MD, PhD, Medical Director, Cardiac Intensive Care Unit, The Cardiac Center, The Children's Hospital of Philadelphia, 34th St and Civic Center Blvd, Philadelphia, PA 19104. (Email: tabbutt{at}email.chop.edu).

	Abstract

Top Abstract Introduction Materials and Methods Results Discussion Conclusions Appendix A Appendix B References

 
Objective: The hospital course for pediatric coarctation repair has not been described. We had 4 aims: (1) to determine the influence of age, anatomy, and type of repair on aortic crossclamp time, (2) to determine the impact of age or aortic crossclamp time on postoperative morbidity, (3) to describe current antihypertensive strategies, and (4) to describe antihypertensive medications at hospital discharge.

Methods: Data were obtained from a prospective randomized multicenter esmolol safety and efficacy trial. The study included patients who were scheduled for a coarctation repair receiving esmolol as their first-line antihypertensive medication in the operating room (n = 118; weight 2.5 kg and age < 6 years).

Results: (1) Patient age and type of coarctation did not affect the aortic crossclamp time. (2) Younger age, but not aortic crossclamp time, was associated with a significantly longer time to extubation and longer hospital length of stay. (3) A combination of esmolol and sodium nitroprusside (Nipride, Roche, Basel, Switzerland) provided excellent early blood pressure control. (4) At discharge, 64% of patients were receiving antihypertensive medications. Older patients were more likely to be discharged with antihypertensive medication (91% of patients aged 2–6 years, P < .0002).

Conclusion: The study describes a multi-institutional approach to the repair of isolated coarctation in infants and children. Patients repaired by end-to-end anastomosis had shorter aortic crossclamp time, younger patients had longer hospital length of stay, a majority of patients had sodium nitroprusside (Nipride) added to esmolol for early blood pressure control, and older patients were more likely to be discharged with antihypertensive medication.

	Introduction

Top Abstract Introduction Materials and Methods Results Discussion Conclusions Appendix A Appendix B References

 
Surgical results are excellent for repair of coarctation of the aorta.^1,2 Postoperative hypertension in these patients is a well-recognized phenomenon, and there are small cases series addressing the efficacy of antihypertensive medications.^3-6 We utilized a multicenter esmolol safety and efficacy trial to obtain surgical and perioperative data in infants and children aged less than 6 years undergoing repair of coarctation of the aorta via a lateral thoracotomy.⁷ We had 4 specific aims from this multi-institutional pediatric population: (1) to determine the influence of age, anatomy, and type of repair on aortic crossclamp time, (2) to determine the impact of age or aortic crossclamp time on postoperative morbidity, (3) to describe current antihypertensive strategies and their ability to control blood pressure in the early postoperative period, and (4) to describe the frequency and type of antihypertensive medications at the time of hospital discharge.

	Materials and Methods

Top Abstract Introduction Materials and Methods Results Discussion Conclusions Appendix A Appendix B References

 
Data were obtained from a prospective randomized multicenter (Appendix A) industry-sponsored esmolol safety and efficacy trial and a physician investigator-initiated substudy.⁷ The primary study was Food and Drug Administration approved and monitored, in addition to being approved by the individual institutions' institutional review boards. The patient population included infants and children who weighed more than 2.5 kg, were aged less than 6 years, and were scheduled for a coarctation repair via a lateral thoracotomy between August of 2000 and November of 2002, whose parent or legal guardian signed informed consent. Exclusion criteria included hypoglycemia, sensitivity to beta-blockers, low resting heart rate, depressed ventricular function, and abnormal screening laboratory results (Appendix B). A total of 164 patients met inclusion criteria, and informed consent was obtained. The final inclusion criterion was hypertension requiring treatment (neonate, systolic blood pressure [SBP] 80 mm Hg; infant, SBP 85 mm Hg; child, SBP 95 mm Hg) within 30 minutes of crossclamp release. A total of 118 patients (72 %) met the SBP criteria within 30 minutes of crossclamp release and received as their first-line antihypertensive a blinded esmolol bolus (125, 250, or 500 µg/kg) immediately followed by an esmolol infusion at the same dose per minute (125, 250, or 500 µg/kg/min) for a minimum of 15 minutes while in the operating room. There was no placebo control. After 5 minutes, additional antihypertensive medications could be added. After 15 minutes, changes in antihypertensive strategies were at the discretion of the practitioners. The results of the esmolol safety and efficacy trial are described elsewhere.⁷

Data presented were prospectively collected during the trial and include patient demographics, mode of diagnosis, associated cardiac lesions, preoperative clinical status, preoperative blood pressure gradient, surgical data, postoperative blood pressure gradients, intensive care unit (ICU) course, and use of antihypertensive agents. Blood pressure and heart rate were recorded hourly in the ICU for the first 12 hours and every 2 hours for the subsequent 12 hours.

Data analysis proceeded in 4 discrete steps. (1) Descriptive statistics were generated for the entire sample, focusing on preoperative, operative, and postoperative factors. (2) The association between age and crossclamp time with postoperative continuous variables was assessed using the Spearman correlation coefficient given the skewed nature of the distributions. For comparisons between these 2 factors and dichotomous variables, the Wilcoxon rank-sum test was used. (3) Several separate logistic regression models were specified and tested to estimate the relationship of age and crossclamp time with postoperative morbidities. (4) Logistic regression modeling was additionally used to estimate the relationship among age, crossclamp time, and postoperative antihypertensive treatment with discharge with antihypertensive medication. All data were analyzed using SAS 9.1 (SAS Institute, Cary, NC).

	Results

Top Abstract Introduction Materials and Methods Results Discussion Conclusions Appendix A Appendix B References

 
Preoperative
Patient demographics and associated anomalies are listed in Table 1 . The median age was 4.8 months (0–84 months). Three patients (2.5%) had previous cardiac surgery, all of which were coarctation repairs. Preoperative diagnostic imaging included echocardiogram in 114 patients (97%) and magnetic resonance imaging in 20 patients (17%). The ductus arteriosus was patent in 30 patients (26%), but only 1 patient was receiving prostaglandins. Eight patients (7%) were mechanically ventilated preoperatively. Preoperative laboratory values included a median blood urea nitrogen of 9 mg/dL (3–21 mg/dL), creatinine of 0.4 mg/dL (0.2–1.2 mg/dL), and hemoglobin of 12 g/dL (9–18.6g/dL).

Intraoperative
Operative times are shown in Table 2 . Intraoperative description of the type of coarctation by the surgeon was discrete (10 mm) in 82 patients (69%) and long segment (>10 mm) in 36 patients (31%). There was no significant difference in crossclamp time between discrete (median 18 minutes, 8–61 minutes) and long segment (median 16 minutes, 6–30 minutes, P = .19) coarctation. The type of surgical repair described by the surgeon and associated crossclamp times are shown in Table 3 . Aortic crossclamp times were significantly shorter for resection with end-to-end anastomosis (n = 107, median 16 minutes, 6–31 minutes) compared with other repairs (n = 11, median 28 minutes, 12–61 minutes, P = .001). The length of aortic crossclamp time was not associated with patient age (P = .73).

SBP gradient (right arm to a lower extremity) obtained 24 hours after arrival to the ICU was 7 ± 13 mm Hg, which was significantly lower compared with 33 ± 23 mm Hg in the operating room before induction of anesthesia (P < .001).

Antihypertensive Therapies
After 15 minutes of esmolol in the operating room, the protocol allowed the routine use of antihypertensive medications at the discretion of the care team. Therefore, the choice of antihypertensive agent in the ICU was independent of the protocol, but many centers may have chosen to continue the blinded esmolol after reaching therapeutic goals. The frequency of esmolol and sodium nitroprusside (Nipride) use during the first 24 hours in the ICU with associated SBP is shown by age groups in Figure 1 . All patients who arrived in the ICU were receiving esmolol, and 61 patients (59%) were also receiving sodium nitroprusside (Nipride). The use of a combination of esmolol and sodium nitroprusside (Nipride) on arrival to the ICU was more common in older children (30 days of age 27% [8/30]; >30 days and <2 years 54% [28/52]; 2–6 years 69% [25/36]). The need for antihypertensive infusions during the first 24 postoperative hours increased with older age. This was true for the number of hours that patients were treated with esmolol (n = 118; correlation coefficient 0.38; P < .001), hours treated with sodium nitroprusside (Nipride) (n = 71, correlation coefficient 0.33, P = .005) or hours treated with either esmolol or sodium nitroprusside (Nipride) (n = 118, correlation coefficient 0.49, P < .001). During the first 24 hours in the ICU, both infusions were gradually reduced and intermittent antihypertensive medications (both intravenous and oral) were introduced. At the end of the first 24 hours, 43 patients (36%) were receiving esmolol and 28 patients (24%) were receiving sodium nitroprusside (Nipride). This strategy provided excellent blood pressure control (Figure 1). Mean SBP during the first 24 hours was 83 ± 3 mm Hg for 30 days of age or less, 103 ± 5 mm Hg for more than 30 days and less than 2 years, and 116 ± 3 mm Hg for 2 to 6 years. The median duration of esmolol and sodium nitroprusside (Nipride) use after arrival in the ICU was 19.9 hours (0.3–80.7 hours) and 18.7 hours (0.4–99.8 hours), respectively. The median maximum dose of esmolol was 521 µg/kg/min (125–9333 µg/kg/min), and the median maximum dose of sodium nitroprusside (Nipride) was 3 µg/kg/min (0.5–8 µg/kg/min). There was a trend toward a higher maximum esmolol dose per unit body weight (mg/kg/min) in older patients (Spearman correlation coefficient 0.17, P = .07).

View larger version (29K): [in this window] [in a new window]   Figure 1. Percentage of patients receiving esmolol and sodium nitroprusside (Nipride, Basel, Switzerland) infusions (left axis) during the first 24 hours after arrival in the ICU is shown with mean SBP for the age group cohort (right axis). A, Patients aged less than 30 days, n = 30. B, Patients aged between 30 days and 2 years, n = 52. C, Patients aged between 2 and 6 years, n = 36. ICU, Intensive care unit; SBP, systolic blood pressure.

View larger version (18K): [in this window] [in a new window]   Figure 2. Percentage of patients receiving intermittent antihypertensive medications (left axis) during the first 24 hours after arrival in the ICU is shown with mean SBP for the age group cohort (right axis). Medications were categorized as beta-blockers (atenolol, labetolol, and propranolol); angiotension-converting enzyme inhibitors (enalaprilat, enalapril, and captopril); calcium channel blockers (nicardipine and nifedipine); and alpha agents and vasodilators (phenoxybenzamine, clonidine, hydralazine). A, Patients aged less than 30 days, n = 30. B, Patients aged between 30 days and 2 years, n = 52. C, Patients aged between 2 and 6 years, n = 36. ICU, Intensive care unit; BB, beta-blocker; ACEI, angiotensin-converting enzyme; CCB, calcium channel blocker; AA, alpha agent and vasodilator; SBP, systolic blood pressure.

	Discussion

Top Abstract Introduction Materials and Methods Results Discussion Conclusions Appendix A Appendix B References

Recently reported surgical approaches via a thoracotomy vary from subclavian flap approach⁸ to end-to-end or extended end-to-end anastomosis.^1,2,10 In this multi-institutional population (n = 107), 91% of patients had an end-to-end anastomosis with the coarctation described by the surgeon as discrete (<10 mm) in 69% of patients. Aortic crossclamp time was not significantly influenced by patient age or type of coarctation (discrete vs long-segment). The aortic crossclamp time was significantly shorter for the end-to-end anastomosis compared with other types of surgical repairs (P < .001).

Blood pressure was well controlled in the postoperative period. The mean blood pressure gradient was reduced from 34 ± 22 mm Hg to 7 ± 14 mm Hg, similar to previously reported values.¹⁰ Thirty percent of patients underwent endotracheal extubation in the operating room, with a median time to extubation of 7 hours (0–352 hours). The median time to hospital discharge was 4 days (2–80 days). Younger age was associated with a longer time to extubation (P < .001) and longer hospital length of stay (P < .001). Aortic crossclamp time was not associated with time to extubation or hospital length of stay.

Postoperative hypertension is well recognized,^11-13 even in neonates.¹⁴ This has been attributed to abnormal elastic properties as demonstrated by echocardiography both before and after repair in newborns¹⁵ and abnormalities in autonomic function, including diminished heart rate variability.^12,14 It is uncertain whether these physiologies relate to the observed late hypertension.^16,17

Therapies for immediate postoperative hypertension are varied with a small case series in the literature.^3-6 This patient population provides a multi-institutional overview of the current antihypertensive strategies used after surgical coarctation repair in infants and children in North America, with a bias toward the use of esmolol. All patients arrived in the ICU receiving esmolol, and 59% of patients were also receiving sodium nitroprusside (Nipride). The use of antihypertensive medications increased with patient age.

At the time of discharge (5 ± 7 days), 64% of patients were receiving antihypertension medications. Neither the maximum esmolol nor sodium nitroprusside (Nipride) dose was associated with the need for discharge with antihypertensive medication. However, patients requiring both esmolol and sodium nitroprusside (Nipride) infusions rather than a single infusion were more likely to be discharged with antihypertensive medication. Older patients were more likely to require medications (P < .0002). Only 17% of infants (5/30) aged 30 days or less were discharged with antihypertensive medications, with all but 1 patient receiving an ACEI. However, 92% of children (33/36) aged 2 to 6 years were discharged with antihypertensive medications, with half receiving ACEI and 40% receiving a beta-blocker or combination of beta-blocker and ACEI.

Study Limitations
This study included only patients who gave informed consent, met blood pressure criteria, and received intraoperative esmolol. Patients described in this study were treated at institutions that are likely biased toward the use of esmolol. The use of blinded esmolol may likely have influenced the early choice of antihypertensive medications.

	Conclusions

Top Abstract Introduction Materials and Methods Results Discussion Conclusions Appendix A Appendix B References

 
This is the first study to describe a multi-institutional approach to surgical repair of coarctation of the aorta in pediatrics. There was no mortality, neurologic complications, or clinically significant mesenteric ischemia. (1) Patient age and type of coarctation did not affect aortic crossclamp time, but those undergoing a resection and end-to-end anastomosis (91%) had a significantly shorter crossclamp time. (2) Younger patient age, but not aortic crossclamp time, was associated with a significantly longer time to extubation and longer hospital length of stay. (3) All patients arrived in the ICU receiving esmolol, and an additional 59% of patients were also receiving sodium nitroprusside (Nipride) (69% of those aged 2–6 years). (4) At the time of discharge, 64% of patients were receiving antihypertensive medications, with angiotension-converting enzyme inhibitors and beta-blockers most commonly used. Older patients were significantly more likely to be discharged with antihypertensive medication (91% of patients aged 2–6 years).

	Appendix A

Top Abstract Introduction Materials and Methods Results Discussion Conclusions Appendix A Appendix B References

 
Participating Centers

United States: Children's Hospital of Philadelphia, Philadelphia, PA, Sarah Tabbutt, MD, PhD, Susan Nicolson, MD; Los Angeles Children's Hospital, Los Angeles, CA, Winfield Wells, MD; Cleveland Clinic Foundation, Cleveland, OH, Paula Bokesch, MD; Children's Hospital of Wisconsin, Milwaukee, WI, James Tweddell, MD; Children's Hospital Boston, Boston, MA, Francis McGowan, MD; Children's Memorial Hospital, Chicago, IL, Carl Backer, MD; TX Children's Hospital, Houston, TX, Steven Stayer, MD; Columbus Children's Hospital, Columbus, OH, Jill Fitch, MD; Children's Hospital of Cincinnati, Cincinnati, OH, David Nelson, MD, PhD; University of MI, Ann Arbor, Mich, Thomas Kulik, MD; San Diego Children's Hospital, San Diego, CA, David Bichell, MD; Hope Children's Hospital, Oak Lawn, IL, Joanne Starr, MD; Duke University, Durham, NC, Scott Schulman, MD; Montefiore Medical Center, Bronx, NY, Gregory Crooke, MD; Denver Children's Hospital, Denver, CO, Dunbar Ivy, MD; Children's National Medical Center, Washington DC, Eric Quivers, MD; University of Iowa, Iowa City, IA, Javier Campos, MD; Children's Hospital of Pittsburg, Pittsburg, PA, Gerard Boyle, MD.

Canada: British Columbia Children's Hospital, Vancouver BC, Suvro Sett, MD; Hospital for Sick Children, Toronto, Glen Van Arsdell, MD.

	Appendix B

Top Abstract Introduction Materials and Methods Results Discussion Conclusions Appendix A Appendix B References

 
Exclusion Criteria

1. The patient has an awake resting heart rate: less than 120 bpm (neonate, 28 days), less than 90 bpm (infant, >28 days and <1 year), or less than 70 bpm (child, 1 year and <6 years).

2. The patient has had reactive airway disease requiring any form of therapy within the past week or requiring hospitalization within the past year.

3. The patient has a known sensitivity to beta-blockers as determined by the investigator.

4. The patient is hypoglycemic (glucose < 60 mg/dL) on their screening laboratory results.

5. The patient has participated in a randomized study or has been exposed to an experimental drug within 28 days before enrollment in this study.

6. The patient has concomitant complex congenital heart disease requiring cardiopulmonary bypass. Hemodynamically insignificant disease (eg, atrial septal defect, ventricular septal defect, or mild pulmonary stenosis) is not reason for exclusion.

7. The patient has had an episode of shock, acidosis, or depressed left ventricular function within 48 hours of surgery, or is receiving dopamine (>5 µg/kg/min) for low cardiac output.

8. The patient's screening laboratory results include the following: hemoglobin < 9 g/dL, platelet count < 100,000/µL, white blood cell count < 1000/µL, creatinine or blood urea nitrogen > 1.5 times the upper limit of normal for age, alanine or aspartate aminotransferase > 2 times the upper limit of normal for age.

9. The patient was previously treated under this protocol.

10. The patient is already receiving a beta-blocker or other long-acting antihypertensive.

	Acknowledgments

 
The authors thank Michelle DeSilvio, PhD, and Xuemei Zhang, MS, for assistance with the statistical analyses.

	Footnotes

 
This study was sponsored by Baxter Healthcare Corporation, New Providence, NJ.

	References

Top Abstract Introduction Materials and Methods Results Discussion Conclusions Appendix A Appendix B References

 

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Sarah Tabbutt Winfield Wells Carl L. Backer James S. Tweddell Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tabbutt, S. Articles by Schreiner, M. Search for Related Content PubMed PubMed Citation Articles by Tabbutt, S. Articles by Schreiner, M. Related Collections Cardiac - physiology Congenital - acyanotic