An Evidenced-Based Review of Emergency Target Blood Pressure Management for Acute Aortic Dissection

Objective To summarize the best evidence of emergency target blood pressure management for acute aortic dissection and provide guidance for evidence-based practice of emergency target blood pressure management. Methods According to the “6S” evidence pyramid model, the evidence of emergency target blood pressure management of acute aortic dissection in various foreign databases and websites of professional associations from January 1, 2010, to August 1, 2022, was retrieved, including clinical decision-making, guidelines, expert consensus, systematic reviews, randomized controlled trials, cohort studies, and case series. Two researchers used the corresponding document quality evaluation tools to evaluate the documents and extracted and summarized the evidence of documents above grade B. Results A total of 17 articles were included, including 6 clinical decision-making articles, 5 guidelines, 2 expert consensus articles, 1 systematic review article, 1 randomized controlled trial article, 1 cohort study article, and 1 case series article, forming 36 best evidences, including 9 topics, which are target value setting, management strategy, disease observation, medical history collection, monitoring methods, vasoactive drugs, nonvasoactive drugs, related examinations, and patient education. Conclusion The best evidence summarized provides a reference for doctors and nurses in the emergency department to manage the emergency target blood pressure of patients with acute aortic dissection. It is recommended that doctors and nurses in the emergency department follow the best evidence summarized to develop individualized target blood pressure management plan for patients.


Introduction
Acute aortic dissection (AAD) refers to a life-threatening aortic disease [1]. Penetrating aortic ulcers, aortic intramural hematoma, and periaortic hematoma are variants of typical aortic dissection [2]. At present, the annual incidence rate of AAD is about 2.8/100000 [3]. About 1/3 of the untreated AAD patients died within the frst 24 hours of the onset, and the mortality rate was more than half within 48 hours [4]. Some studies have shown that the incidence rate of AAD with hypertension is 50.1%∼75.9% [5]. Uncontrolled hypertension not only promotes the progress of dissection but also damages target organs. It is the most important and intervenable risk factor for AAD. Blood pressure management has become the initial treatment for AAD and has been throughout [4]. Some studies show that the 5-year survival rate of AAD patients with poor blood pressure management is about 60%, and that of those with good blood pressure management is as high as 95% [5]. At present, emergency blood pressure management is mostly based on personal clinical experience, and some medical staf are not even aware of the relevant knowledge of AAD blood pressure management and have not developed an individualized target blood pressure management plan for patients based on evidence-based evidence. Te blood pressure management efect of AAD patients has not been signifcantly improved in the past 20 years [5]. In addition, according to the recommendations in the guide, some emergency department doctors are conservative in their medication. Te above factors lead to a low rate of reaching the target blood pressure in emergency treatment and poor efects of blood pressure management [5]. Trough a literature review, it was found that the existing evidence on AAD emergency target blood pressure management is scattered. Terefore, it is necessary to integrate the best evidence of AAD emergency target blood pressure management to provide reliable evidence-based medical evidence support for emergency clinical practice.

Establish the Question.
According to the PIPOST [6] tool, the evidence-based question of this study is constructed, which is, "how to manage the target blood pressure of AAD patients." P (population): patients diagnosed with acute aortic dissection; I (intervention): a series of intervention measures for target blood pressure management; P (professional): medical staf of the emergency department; O (outcome): target blood pressure reaching rate, hospital mortality; S (setting): emergency department of the hospital; and T (type of evidence): relevant guidelines, randomized controlled trials, systematic reviews, and so on.

Retrieval Strategy.
According to the "6S" evidence resource pyramid model [7], the computer searches with the English keywords of "aortic dissection/aortic aneurysm/aortic disease/ aortic syndrome/dissection aneurysm/blood vessel dissection/ intramural haematoma/penetrating atherosclerotic ulcer" and "hypertension/blood pressure management/hypotension/blood pressure control/homeodynamics" in UpToDate, Guidelines International Network (GIN), Scottish Intercollegiate Guidelines Network (SIGN), National Institute for Health and Care Excellence (NICE), Canadian Medical Clinical Practice Guidelines (CPG), WHO, Maimaitong Registered Nurses' Association of Ontario (RNAO), American Heart Association (AHA), European Society of Cardiology (ESC), JBI, Te Cochrane Library, PubMed, Embase, CINAHL, SinoMed, Web of science, and Clinical trials are retrieved from January 1, 2010, to August 1, 2022.

Inclusion and Exclusion Criteria of Literature.
Inclusion criteria were as follows: Te patients were nontraumatic AAD patients aged ≥18 years; the research content was AAD blood pressure management; the types of evidence resources included clinical decision-making, guidelines, expert consensus, systematic reviews, randomized controlled trials, cohort studies, and case series. Exclusion criteria were as follows: the patients were pregnant; the quality of literature was below grade B; articles were published repeatedly or were unable to obtain the full text from; abstracts of the meeting; interpretation or summary of the guide; and updated old guide or expert consensus.

Literature Quality Evaluation Method.
Tis study was independently evaluated by two doctors trained in evidencebased medicine. When the evaluation opinions of the two doctors were inconsistent, the decision was made by consulting evidence-based medicine experts. When the conclusions of evidence from diferent sources confict, this study follows the inclusion principle of high-quality evidence frst, the latest published authoritative literature second, and then the evidence-based evidence [8].
UpToDate belongs to the top resource of the evidence resource pyramid model, and the evidence conforming to the clinical situation is directly used. Te guidelines adopt the AGREE II [9] (Appraisal of Guidelines for Research and Evaluation Instrument) evaluation tool. AMSTAR [10] evaluation tool is used for system reviews. Randomised controlled trials, cohort studies, and case series were evaluated using the corresponding evaluation tools of the Australian JBI Evidencebased Health Care Center Evaluation Standard (2016) [7].

Evidence Grade and Recommended Strength.
Te evidence preclassifcation and evidence recommendation level system (2014) [8] of Australia's JBI Evidence-based Health Care Center was used to determine the evidence level and recommendation strength. According to the type of study, the level of evidence is divided into level 1∼5, and a correspondence expert group (all with evidence-based medicine/ nursing background, including 2 emergency physicians, 4 nurses, 1 cardiac surgeon, and 1 vascular surgeon) is established. Te recommendation strength of the evidence is determined according to the FAME attribute of the evidence (feasibility, appropriateness, clinical signifcance, efectiveness), including level A recommendation (strong recommendation) and level B recommendation (weak recommendation) (Figures 1 and 2).

Literature Quality Evaluation.
(1) A total of fve guidelines were included, including the percentage of standardization in each feld and the quality evaluation of the guidelines (Table 2). (2) Quality evaluation of expert consensus. A total of 2 expert consensus articles were included; all of the items were "Yes." (3) Others include 1 systematic review, and all items are "Yes"; 1 randomized controlled trial, item 9 is "no," 1 cohort study, item 3 is "unclear," 1 case series, item 7 is "unclear," and the other items are "yes.") (Te items in Figure 4) ( Table 3) 3.3. Summary of Evidence. Trough the extraction and integration of evidence, we fnally summarized the evidence from 9 aspects, including target blood pressure setting, A-level recommendation: Strong recommendation B-level recommendation: Weak recommendation 1. Clearly show that the intervention does more good than harm or does more harm than good 2. High-quality evidence supports the application 3. Favorable or no impact on resource allocation 4. The patient's values, wishes, and experiences are taken into account 1. The evidence is unclear that the benefits of interventions outweigh the harms or the harms outweigh the benefits 2. There is evidence to support the application, but the quality of the evidence is not high enough 3. Beneficial but small or no impact on resource allocation 4. Partly taking into account the patient's values, wishes, and experiences

Discussion
Tis study analyzed and recommended evidence from the following three aspects: target blood pressure setting and management strategies; vascular active drugs and other relative drugs; and patient education. Evidence from this study (1)(2)(3)(4)(5)(6)(7)(8) indicated that the doctors in the emergency department need to develop initial target blood pressure values, time to reach target values, and target blood pressure management strategies based on individual diferences in patients. Te initial treatment of AAD is to quickly stabilize the patient's hemodynamics under tolerable conditions [2,27] and slow down the progression of the disease by reducing blood pressure and heart rate. Hypertension will lead to the rupture of the dissection, while Hypotension will afect the blood supply of important organs, so the systolic pressure should be kept within the ideal range of 100∼120 millimetre of mercury [2]. Tere is evidence to suggest that blood pressure <120/80 mmHg and heart rate <60/min during conservative treatment are benefcial for patient prognosis [11]. For patients with AAD rupture and hemodynamic instability, the systolic blood pressure level (80∼100 mmHg) is maintained at a low level, that is, the allowable hypotension [15], while ensuring adequate organ perfusion. Unlike hypertension management strategies that combine other diseases, AAD patients need to quickly (20-30 minutes) reduce blood pressure to the safe target range while ensuring sufcient organ perfusion [27,28]. In addition, when making clinical decisions, it is also necessary to consider factors such as the patient's and their family members' attitudes towards treatment and expectations for prognosis. By establishing an efcient and cooperative multidisciplinary diagnosis and treatment team (including an emergency medical team, cardiac surgery, vascular surgery, and imaging department), the emergency quality of AAD patients can be improved [29].
Te evidence of this study (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) emphasized that AAD patients should receive monitoring and treatment in the emergency department. Emergency physicians closely observe to avoid potential factors that afect blood pressure changes and efectively reduce related complications and mortality [30]. Studies have found that poor visceral perfusion is an important complication of AAD [31]. For example, low back pain with a sudden decrease in urine output or an increase in creatinine often involves renal artery dissection. Hypotension often indicates cardiac tamponade, abdominal pain, and an increase in lactic acid with or without melena are manifestations involving Mesentery arteries, which should be given sufcient attention by emergency physicians. Te high-risk signs of AAD are pulse pressure diference of both upper limbs >20 mmHg [32], hypotension, asymmetric pulse intensity of both upper limbs, or disappearance of one side [16]. Emergency doctors can also evaluate the progress of the anatomy through dynamic observation. It is also important to guide the development of blood pressure management plans by collecting information about whether patients have a high-risk medical history and a special medication history. In terms of monitoring methods, it is necessary to measure the blood pressure of the patient's limbs. Invasive arterial blood pressure monitoring can quickly identify changes in patients' blood pressure [16], which has important clinical signifcance for observing the condition and adjusting     (2) Initial target: Strict target heart rate <60/min or loose target heart rate <80/min, systolic blood pressure 100-120 mmHg or <130/80 mmHg (in combination with diabetes or chronic renal failure); for hemodynamically unstable AAD ruptures, maintain systolic blood pressure. 130/80 mmHg (in combination with diabetes mellitus or chronic renal failure); for hemodynamically unstable AAD ruptures, maintain systolic blood pressure 4 A (3) Te recommendation is to reduce to the initial target value within 20-30 min while ensuring organ perfusion 5 B Management strategy (4) Initial treatment is blood pressure and heart rate control 5 B (5) Te "hypotensive haemostasis" strategy of restrictive fuid resuscitation is recommended for the haemodynamically unstable 1 A (6) Emergency surgery recommended for AAD rupture and hemodynamic instability 1 B (7) Decision-making must be individualised, taking into account patients' coexisting conditions (e.g., stroke, renal failure, and diabetes), age and the expectations of patients and families Although there is evidence that pulmonary artery foating catheter and central venous pressure monitoring can be used when patients have serious hemodynamic disorders, this requires a certain level of professional skills and preparation time and is not recommended as an emergency monitoring method [19]. Te evidence in this study (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31) elucidated the selection and considerations of drugs. In drug selection, β receptor blockers are the frst choice for the treatment of AAD [32], except for contraindication such as asthma and atrioventricular block. If using β receptor blockers still cannot achieve the expected antihypertensive goals, it is recommended to [4,25] use two or more antihypertensive drugs together, such as urapidil, sodium nitroprusside, and diltiazem, to achieve the goal of rapid hypotension. Emergency doctors need to evaluate whether there are contraindication when selecting drugs. Te medication method is micropump intravenous maintenance. During the medication process, close attention should be paid to whether there are any adverse reactions. Te choice of drugs for hypotension patients is very limited and must be used with caution. At the same time, actively search for the causes of hypotension and closely observe the changes in the condition [20]. Te severe pain caused by AAD can lead to the release of endogenous neurotransmitters in the patient's Emergency Medicine International body, leading to increased blood pressure and poor subjective experience. Terefore, morphine, pethidine, and other powerful analgesics should be given actively [21]. Some studies have shown that traditional Chinese medicine can also be used as an auxiliary drug for AAD blood pressure management, but it has not been widely used in clinical practice and is not recommended for emergency treatment [32]. Te evidence from this study (32)(33)(34) clearly describes that emergency physicians should select the best diagnostic method based on the patient's hemodynamic status through careful and rapid comprehensive evaluation. Tis can not only quickly determine whether the target organs such as the kidney and intestine are damaged but also determine the location and extent of aortic dissection. In addition, there is evidence (35-36) that emergency physicians should provide patients with a comfortable diagnosis and treatment environment, necessary disease-related knowledge education, and psychological intervention, fully utilize a good social support system, alleviate negative emotions such as fear and anxiety, and avoid excessive blood pressure fuctuations. Meanwhile, smoking is the second largest risk factor for AAD, and strict smoking cessation interventions should be carried out for patients [31,32]. Guide them to stay absolutely in bed and reduce behaviors that lead to chest and abdominal pressure and elevated blood pressure, such as forced coughing and defecation.

Limitations
Due to limitations or potential bias in individual studies, the assessment tools we used did not allow for such individual studies and could only target most of the literature. In addition, due to limitations of the review process, it could not address potential publication bias or the possibility of missing relevant studies.

Conclusion
Tis study summarizes the best evidence for target blood pressure management in an AAD emergency. Tis study provides the best strategy for blood pressure management. At the same time, the doctors and nurses in the emergency department should also consider the patient's situation and the family's expectations in an all-round way, formulate an individualized target blood pressure management plan, fully analyze the factors that promote and hinder the application of the evidence, and prudently apply the evidence to the clinic. In addition, emergency management personnel should actively improve and standardize blood pressure management rules and regulations, carry out training, and promote the transformation of knowledge and skills into practice.

Conflicts of Interest
Te authors declare that they have no conficts of interest.