Efects Of Dexmedetomidine On Surgery For Type A Acute Aortic Dissection Outcome

Acute type A aortic dissection is a life-threatening true surgical emergency. Despite aggressive operation and technique advances, surgical mortality is still high. According to the German Registry for Acute Aortic Dissection Type A (GERAADA), from 2006 to 2010, 2137 patients were surgically treated for acute type A aortic dissection with an overall 30-day mortality of 16.9%1. Another report from the International Registry of Acute Aortic Dissection (IRAD) shows, over time, from 1995 to 2013, the in-hospital surgical mortality rate of patients with type A aortic dissection dropped significantly from 31%, but still as high as 22%2. Acute type A aortic dissection also accompanies several major complications, including shock, tamponade, visceral ischemia, peripheral ischemia, and brain injury. Besides, minor complications including acute kidney injury, delirium, atrial fibrillation, and respiratory failure also occur commonly after the operation. Cardiopulmonary bypass (CPB) causes inflammation throughout the body, leading to organ dysfunction3. Research also showed an inflammatory mechanism is involved in medial degeneration and its association with the clinical manifestations of aortic dissection4. 

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Dexmedetomidine is a central α-2 adrenergic agonist, which has been shown to have anti-inflammatory properties, decreasing mortality and attenuating plasma cytokine concentrations in laboratory animals5. Dexme-detomidine infusion reveals anti-inflammatory effects during and after CPB. These suppressive effects of dexmedetomidine might be due to the inhibition of nuclear factor kappa B activation and suggest that intra-operative dexmedetomidine may beneficially inhibit inflammatory responses associated with ischemia–reperfusion injury during cardiopulmonary bypass6. A meta-analysis published in 2015 shows that perioperative use of dexmedetomidine as an adjunct to general anesthesia leads to signifcant decreases in serum levels of IL-6, IL-8, and TNF-α within a period of 24 h postoperatively7

We hypothesized that dexmedetomidine may provide cardiac, brain, pulmonary, and renal protection for acute type A aortic dissection patients. This study aimed to investigate the effect of dexmedetomidine on the outcome of acute type A aortic dissection. In addition to investigating the endpoints of death, this study also examined the potential impact of dexmedetomidine on other major endpoints such as stroke, respiratory failure, fasciotomy or amputation, ECMO, postoperative infection, acute kidney injury, newly-onset dialysis, and acute respiratory distress syndrome during the postoperative period for patients undergoing surgery for acute type A aortic dissection.

Methods 

Data source. 

This study was executed using data from the Chang Gung Research Database (CGRD) in Taiwan. The CGRD contains the multi‐institutional standardized electronic medical records (EMR) from Chang Gung Medical Foundation (CGMF) from seven Chang Gung Memorial hospitals (CGMH), including two medical centers, two regional hospitals, and three district hospitals from northern to southern Taiwan. The EMR contains the patient‐level data derived from electronic medical charts of patients established for administrative and health care purposes for CGMH. All the healthcare providers from CGMH can access the data for their clinical practice. The Department of Information Systems Management of CGMH integrated and standardized all EMRs from CGMH without selecting criteria and established CGRD for research purposes. The basic architecture for the CGRD includes most of the information from EMR for routine epidemiologic health care studies, with nine profiles for laboratory data, inpatient data, outpatient data, emergency patient data, pathological data, nursing data, charge data, disease category data, and surgery data8. The CGRD has collected the EMR of all patients from CGMH since 2000. Specifically, the health conditions are coded following the International Classification of Disease, 9th Revision Clinical Modification (ICD‐9‐CM) codes before 2016, and ICD‐10 codes afterward. Te study was approved by the institutional review board (IRB) of Chang Gung Memorial Hospital and informed consent was waived. All research was performed by the Declaration of Helsinki concerning the ethical principles for medical research. All methods were carried out by relevant guidelines and regulations.

Study population.

The study cohort flowchart is shown in Fig. 1. This is a retrospective multi‐institutional cohort study. Patients hospitalized after surgery for acute type A aortic dissection between January 1, 2014, and December 31, 2018, were studied. Patients with a Taiwanese NHI procedure code for ascending aortic replacements (69,024, 68,043) were used for analysis. Patients who had duplicated surgical reports were excluded. Te Patients who died within 24 h after the operation were also excluded. All surgical reports were reviewed by two cardiac surgeons to make sure the enrolled patients had acute type A aortic dissection. The patients were then divided into two groups: the dexmedetomidine group and the non-dexmedetomidine group. The deemed to midine group was identified by using the medication supply code (BC24002212) in the post-operative periods for up to 24 h.

Comorbidities and outcomes.

Demographic data, clinical characteristics, and comorbidities were identified using ICD-9-CM or NHI procedure codes. Pre-operative lab data, post-operative lab, and surgical data were all derived from medical records. Perioperative outcomes were detected by tracing patients’ hospitalization records. Outcomes of interest are the primary composite outcome and in-hospital mortality. Components of the primary composite outcome were all-cause mortality, acute kidney injury, delirium, postoperative atrial fibrillation, and respiratory failure. The severity of acute kidney injury was categorized by Acute Kidney Injury Network (AKIN) criteria which was endorsed by the Kidney Disease Improving Global Outcomes (KDIGO) Clinical Practice Guideline. Hemodialysis was defined by the Taiwan NHI reimbursement code for hemodialysis or continuous venovenous hemofiltration dialysis (58,001 or 58,018) Delirium was defined by positive CAM-ICU score evaluated by ICU nurse, use of haloperidol for agitated delirium, and confrmed by neurologist consultation. Postoperative atrial fibrillation was defined by reviewing of EKG report, using amiodarone for rhythm control, and reviewing discharge notes. Respiratory failure was identified using ICD-9-CM diagnostic codes. Patients were followed until death or December 31, 2018, whichever came first.

Statistical analysis. Due to a substantial number of missing observations in the laboratory and surgical data, we frst imputed the missing values using the single expectation maximization (EM) imputation method and then created the propensity score matching (PSM) cohort. The PSM by multivariable logistic regression model was conducted to balance the baseline characteristics between the dexmedetomidine and non-dexmedetomidine groups. Each dexmedetomidine case was matched to two counterparts in the non-dexmedetomidine group if possible. The parameters used to calculate the propensity scores were age, sex, previous cardiac surgery, comorbidity, pre-operative condition, pre-operative lab data, surgical data, and surgical extension (listed in Table 1). The greedy nearest neighbor algorithm was adopted with a caliper width of 0.05 standard deviation of the logit of the propensity score. An absolute standardized difference (STD) of less than 0.2 after matching was considered to indicate a small difference between the groups. After matching, 72 and 14 patients in the dexmedetomidine had two and one counterparts respectively, resulting in a total of 86 patients with dexmedetomidine and 158 patients without dexmedetomidine. Our statistical analysis methods have been described before. In detail, the in-hospital outcomes between the dexmedetomidine and non-dexmedetomidine groups were compared using a generalized estimating equation (GEE), in which the robust standard error was estimated to account for the outcome dependency within the same matched pair. When the link was identified, the distribution was normal for continuous outcomes. When the link was logit, the distribution was binomial for binary outcomes. Te study group was the only explanatory variable in the aforementioned regression analyses. Any two-sided P-value that was less than 0.05 was considered to be statistically signifcant, and no adjustment of multiple testing (multiplicity) was made in this study. Statistical analyses were performed using SAS version 9.4 (SAS Institute, Cary, NC), including the procedures of “patch” for PSM and “genome” for GEE.

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