Throughout the time period studied, the total number of anesthetics with dexmedetomidine increased each year (Table 4). However, there was wide variation among participating centers with respect to the frequency of dexmedetomidine use. Some centers did not use dexmedetomidine for any of their cardiovascular operations. Other centers performed >90% of all their anesthetics with the drug. This variability did not seem to be specifically related to center volume (Figure 1), and centers also demonstrated variability over time with respect to their dexmedetomidine use (Figure 2).
CHD is one of the most common anomalies at birth, with an incidence of 4 to 8 per 1000 births.18 Advances in surgical, anesthetic, and ICU management have greatly improved outcomes. However, CHD is still implicated in 30% to 50% of infant mortality because of congenital anomalies.19 Importantly, CHD is a significant risk factor for anesthesia-related cardiac arrests.20 Many more patients suffer morbidities, such as arrhythmia requiring a pacemaker, neurologic deficits, renal injury, prolonged mechanical ventilation, mechanical circulatory support, and reoperation. Developing new medications and techniques to reduce these risks remains a priority in the perioperative care of this patient population. During the last several years, dexmedetomidine has found an increasing role in the perioperative management of children with CHD, as familiarity with its potential benefits and side effects become better known.
A number of published studies describe the clinical use of dexmedetomidine in pediatric congenital heart patients during surgical repair and in the cardiac ICU. The medication is effective and well tolerated in these patients.4–7 Patients receiving dexmedetomidine have been observed to require less opioid and benzodiazepine medications.6,7 Treatment with dexmedetomidine in associated with deeper levels of sedation and a decreased time to extubation.3 Patients receiving dexmedetomidine have also demonstrated an attenuated hemodynamic and neuroendocrine response to surgery and cardiopulmonary bypass.21,22 The drug has also been used for its antiarrhythmic properties.23,24 In addition, a number of animal studies are beginning to examine the role of dexmedetomidine in inhibiting inflammation, attenuating ischemic-reperfusion injury, and potentially providing neuroprotection during anesthesia.25–31
Despite the growing number of clinical studies, these generally involve small sample sizes and do not report on the clinical outcomes of this patient population. A study by Fuhai et al.9 involved a much larger subject group and reported that mortality and major morbidity are improved in adult patients undergoing cardiac surgery who receive dexmedetomidine. However, the adult cardiac population is physiologically very different from the pediatric patients with CHD. Thus, this very good study cannot be extrapolated to children. Furthermore, though there are a number of animal studies that suggest that dexmedetomidine may serve a protective role in the inflammatory and ischemic-reperfusion injury pathways that occur with bypass, it is too soon to translate these experiments to the bedside and patient outcome.
Our study is unique in that it represents the first time a group of anesthesia patients was analyzed from the CCAS-STS—Congenital Heart Disease Database. The >12,000 patients, from 29 medical centers, represent a uniquely large sample size for a study examining the use of a specific medication in the anesthetic management of children with CHD. Our data show that dexmedetomidine is used in a large percentage of children undergoing cardiopulmonary bypass for surgical repair of CHD, with 30% of our patient population treated with dexmedetomidine. The data also demonstrate that dexmedetomidine use increased during the time period of our study. Consistent with their lower risk, patients in the DEX group had lower mortality rates in comparison with the NoDEX group. In addition, patients treated with dexmedetomidine were less likely to experience complications after surgery. They were separated from mechanical ventilation and extubated sooner, although we do not know whether they were extubated while still receiving the medication. The DEX patients spent less time in the hospital than patients who did not receive dexmedetomidine.
However, the pediatric congenital heart patient population is a very heterogeneous group, with widely variable expected outcomes because of differences in the severity of the defect, the age at which the patient is operated on, and the likelihood of other comorbidities such as preexisting neurologic injury. Analysis of the data demonstrates that dexmedetomidine was preferentially given to older and larger patients. There also seems to be a preference in using the drug in patients who were at less risk of suffering a perioperative death, based on the lower STAT mortality level in the DEX group. The DEX patients seemed to undergo less complex surgery, as reflected in their procedural complexity scores, as well as their lower aortic cross-clamp times and circulatory arrest times.
Although one of the original objectives of this study was to evaluate the impact of dexmedetomidine use on outcomes, including perioperative mortality, major morbidity, and propensity for arrhythmia, our initial exploratory analysis demonstrated that patients receiving DEX underwent lower complexity procedures and had a lower risk of mortality. Despite several attempts, we were unable to appropriately balance the groups for a meaningful multivariable analysis; there were simply too many unknowns regarding the patient-, provider-, and center-level factors that contribute to dexmedetomidine use.
There are inherent limitations in using a large database to answer clinical questions such as ours. First, all such research is retrospective in design. Second, the CCAS-STS database is voluntary and is not a random sample of pediatric hospitals. In addition, we were unable to consider dose or duration of drug administration in our analysis, because this information is not captured in the database. We also did not have the capability to analyze the data based on different surgeons. Although the STS conducts random audits of their surgical participants annually, the CCAS currently lacks audit or data verification for the anesthesia component of the registry. For the timeframe analyzed in this cohort, the CCAS-STS registry was in its infancy. As with any new registry, there is a learning curve for centers as they develop the resources needed to ensure high-quality data submission. For these reasons, we excluded centers with high levels of missing data (n = 8) as well as patients with missing data for key variables. In total, nearly half of the records in the registry were ineligible for inclusion in the analysis. Although exclusions are standard practice for any registry-based analysis, this does introduce the possibility of some bias when generalizing these data to the broader spectrum of centers performing cardiac anesthesia. As the CCAS-STS database matures, data quality would be expected to improve, and future analyses may provide a broader perspective.
Finally, pediatric cardiac surgery patients cover a wide range of age and size and undergo many different types of surgery with a wide range of illness severity and surgical complexity. When looking at outcomes, a first glance appears to suggest an improvement in mortality and morbidities in the DEX group. However, because of the differences in patient and surgical characteristics in each study group, and our inability to statistically adjust for confounding variables, we are unable to conclude that dexmedetomidine provides any improved outcomes for pediatric CHD patients having cardiopulmonary bypass surgery.
Despite the limitations of this study, we are able to describe the growing use of dexmedetomidine in children anesthetized for surgical repair of CHD. For the time epoch in our study, dexmedetomidine appears to be preferentially given to older and larger children who are undergoing less complex CHD surgery. Although the use of dexmedetomidine in the anesthetic management of CHD surgery has been increasing annually, there is wide center variability in use, and the drug has not been adopted by all anesthesiologists who care for these patients. Furthermore, there appears to be some reluctance to give dexmedetomidine to younger, smaller patients who are facing more complex surgery and are at a higher risk of death. Although we did not investigate the reasons for this discrepancy, one can conjecture that, with growing knowledge and experience, dexmedetomidine may find its way into an expanding patient population. We believe that this study is the largest investigating the use of an anesthetic drug in CHD patients. It is also the first analysis of the anesthesia data in the CCAS-STS Congenital Heart Disease Database. This registry continues to expand by tens of thousands of patients annually. Perhaps with continued growth, a larger population in the data set will allow future analyses to comment on outcomes associated with dexmedetomidine use with greater confidence and potential subgroup analysis in types of surgery, such as repair of Tetralogy of Fallot, which are associated with specific adverse events, such as postoperative arrhythmias, for which dexmedetomidine may be particularly useful.
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