Reflections on dexmedetomidine as an optimum therapy for emergence delirium in the elderly with emergency abdominal surgery

Introduction

Postoperative mental and behavioral abnormalities are generally divided into three situations: emergence delirium (DE), postoperative delirium (POD), and postoperative cognitive dysfunction (POCD). Table 1 presents their clinical manifestation and onset time. ED is an acute cognitive change characterized by fluctuations in consciousness and attention during the recovery period immediately after anesthesia, which is what anesthesiologists and nurse anesthetists (NA) often face. Table 2 lists two kinds of risk factors causing ED (Read MD, Maani CV, et al., 2017; Munk L, Andersen G, et al., 2016). It's easy to infer if being not timely reversed, that ED could prolong the time of delirium and cognitive impairment. Delirium leads to longer hospital stays, loss of independence, decreased cognitive function, increased risk of falls, pressure ulcers, readmission, and even accidental death, especial for the patients with angiocardiopathy (Zywiel MG, Hurley RT, et al., 2015; Witlox J, Eurelings LSM, et al., 2010). While, in the post post-anesthesia care unit (PACU), adverse events include mainly accidental extubation, the injury of medical care, and falling and so on. Therefore,we are supposed to focus to how to cope with it timely.

Although the majority of ED patients can be released, involved measures include medicines and physical restricts, but are not regulated and consolidated. Besides, ED may further aggravate damages to the nervous system and the cardiovascular system, which leads to forms a vicious circle as confronting with the dysfunction of certain organs, and even increase the risk of multiple organ dysfunction syndromes (MODS). Therefore, the elderly with ED and other complications should not be underestimated. Dexmedetomidine has been well known and popular clinically due to its effect for sedation and the prevention of ED and postoperative behavioral changes in pediatric patients (Shi M, Miao S, et al., 2019), but there is little literature reported about the aged with ED in PACU. Thus, the article analyzed the aspects involved delirium in the patient from the case and explored the role of dexmedetomidine.

Case presentation

An 80-year-old, American Society of Anesthesiologists (ASA) physical status (PS) Ⅲ male with perforation of empty organs, septic shock, acute suppurative peritonitis, and pulmonary infection, an emergency exploratory laparotomy was performed. His medical history was significant for hypertension for more than 20 years, coronary heart disease for 10 years, and gout for 6 years. The white blood cell counts were 9.57×10⁹/L, hemoglobin was 148 g/L, and the neutrophil ratio was 79.7%, urinary sodium was 4036 pg/ml, troponin was 27.8ng/L, and examination in PS revealed a tabular abdomen with muscle tension, which were was usually signs of infection. The creatinine count was 147 μ mol/L, indicating that renal function is impaired. The computerized tomography (CT) of abdomen showed free gas was scattered in the upper abdomen, suggesting digestive potentially tract perforation. Electrocardiogram (ECG) showed fast ventricular rate (heart rate: 138 times/min, blood pressure: 138/106mmHg) and atrial fibrillation. Final diagnoses: Septic shock, Acute Suppurative Peritonitis, Pulmonary Infection with emphysema, Renal Insufficiency, Coronary Heart Disease, Atrial Fibrillation, the level Ⅲ of Hypertension with a high-risk group. During the operation, about 1,000 milliliters (ml) of pale yellow pus was inhaled into the contaminated bottle and the perforated stomach was repaired, and the acid-base imbalance was tested, He underwent anesthesia for 4 hours (h) and surgery for one and half an hour without any noted life-threatening complications.

His medications included enalapril and amlodipine because of hypertension. Induction of general anesthesia was accomplished with etomidate, sufentanil and succinylcholine, followed by successful oral intubation with an endotracheal tube (ETT). Maintenance of anesthesia was accomplished with intravenous (IV) and inhalation anesthetic respectively consisting of remifentanil infusions and sevoflurane inhalations for the duration of this 4-hour procedure. He was also given sufentanil, cisatracuramide and midazolam before incision. Tramadol and sufentanil were used in postoperative analgesia. With regaining spontaneous breathing and confirmed the absence of residual paralysis and no pharmacologic reversal of neuromuscular blockade, the patient was successfully extubated in the operating room (OR). However, the patient was very restless and combative, even his IV channel and urinary duct were violently removed by herself. His Richmond Agitation and Sedation Scale (RASS) score were + 4 at the moment.

Subsequently, he was treated with midazolam, sufentanil and small dose of propofol, and transported to the PACU. On arrival to the PACU, His heart rate (HR) was 138 bpm and his blood pressure (BP) was 138/108 mmHg agitated although not combative. His Richmond Agitation and Sedation Scale (RASS) score were + 2. Attempts were made to verbally reorient the patient unsuccessfully. Pharmacologic interventions including midazolam were also unsuccessful. Finally, upon bringing the patient’s wife into the PACU in an attempt to aid in reorientation, an IV bolus of 0.5 μg/kg of dexmedetomidine was administered for 15 min. An IV infusion of dexmedetomidine was then started at 0.4μg/kg/h, which was titrated off over the ensuing hour. Immediately after the initial bolus of dexmedetomidine. The patient's blood pressure gradually returned to normal and no longer demonstrated any delirium, soon conversing appropriately, with a RASS score of 0. He was monitored in the PACU per standard protocol, and after discharge criteria were met, he was transferred to the ward. This study was approved by the ethics committee of the West China Hospital of Sichuan University.

Discussion

It was described that the successful treatment of ED using dexmedetomidine after general anesthesia in the aged in this case. he received sufentanil, cisatracuramide and midazolam before incision. Maintenance of anesthesia was achieved with volatile and IV anesthetic of the procedures. he also received perioperative opioids (sufentanil and tramadol). All therapies attempted for the patient before administration of dexmedetomidine served as a temporary role when treating pain and excitation with midazolam, sufentanil and propofol after extubation and even, in one instance, bringing a patient’s spouse to bedside. There was an array of acute and chronic complications, many of which are risk factors for the development of ED. But RASS and Aldrete score improved after initiation of therapy with dexmedetomidine (Table 3, 4). The RASS score, an accepted rule to assess agitation and sedation for critically ill patients, is often used in intensive care units (ICU) for aiding in appropriate goal-directed management of patients with ED. Items of the Aldrete scores include Activity, Circulation, Consciousness, Respiration, and Oxygenation, the changes of Circulation, Consciousness were most notable in the patient). In a word, he was calmer after the administration of dexmedetomidine.

Delirium is an acute neuropsychiatric syndrome involving changes in consciousness, attention, cognition and perception. Clinically, there are some simple tools to assess delirium, including Richmond Agitation and Sedation Scale (RASS), the Simple Question in Delirium (SQiD), modified RASS (m-RASS), and Short-CAM and Nursing Delirium Screening Scale (Nu-DESC). However, Nu-DESC provides higher sensitivity and higher specificity than other tools. The Nu-DESC was mainly applied by nurses to manage delirium due to being more easily adaptable in nursing practice in a short period of time (van Velthuijsen et al., 2016). (The Nu-DESC is made of five items, including orientation, behaviour, illusions, communication, and psychomotor retardation. Among them, psychomotor retardation is relatively more important for clinical advantage of a detection of hypoactive delirium. Each item is rated from 0-2, for a total score of 0-10 points, with a cut-off of 2 points (> 1) for delirium). In this case, it is critically significant to evaluate ED because it damages patients more severely (Marchington, Carrier, et al., 2012; Jeong E, Park J, et al., 2020). In fact, the Nu-DESC is supposed to be applied in this case.

In addition, delirium is caused by multiple reasons. According to evidence-based and experts consensus, the predisposing factors and inducing factors of POD were summarized (Table 5, 6) (Aldecoa C, Bettelli G, et al., 2017). The case occurred in patients with advanced age, septic shock, atrial fibrillation and a less detailed history of coronary disease, not to mention emergency surgery, all independent predictors of developing delirium, what was worse, with the dysfunction of lung and acute renal inadequacy, all in all, the patient was at extremely high risk for delirium. As infection and emergency operation occur simultaneously in a patient, the immune system and stress reaction are activated by each other. With the increase of a series of inflammatory mediators, neutrophils can cross the blood-brain barrier, causing that activated oxygen and protease are released to destroy the arrangement of endothelial cells in the central nervous system, which is considered to be one of the potential mechanisms of POD (Van Munster BC, Korevaar JC, et al., 2010; Cortese GP, Burger C., 2017). Previous studies have shown that it makes the older more likely to suffer from POD when cumulative permanent damages to dendrites, neurons, microglia, and receptors and being under physiological stress, thus age is critically associated with delirium (Afonso A, Scurlock C, et al., 2010). It can be inferred delirium a common postoperative complication in the elderly. In addition, for delirium patients, internal environmental disorders (such as dehydration, acid-base imbalance) in the body, and septic shock caused by perforation of cavity organs are also dangerous manifestations. As elevate creatinine or acute renal inadequacy is at least partly due to hypoperfusion of the kidneys and systemic inflammation (Denny DL, Lindseth G., 2017).

As a whole, different tissues and organs constitute different systems, but their role in the body is closely related. When a system does not work properly, it often implicates others. If not processed in time, they are possible to be in a vicious circle by each other. Therefore, it is not difficult to consider that the injured heart function or a sharp of blood volume may impel the representation with delirium, delirium conversely aggravates the instability of hemodynamics (Zipser CM, Deuel J,. 2019). The patient had a long history of coronary heart disease and hypertension, but in detailed, we failed to learn about the patient’s past illness and its effects from patient’s spouse. There is no doubt that cardiac function is difficult to accurately assess, and the patient's tolerance to abdominal surgery is unpredictable, above which increases the risk of anesthesia and surgery and the occurrence of delirium. So, except the symptomatic treatments of perioperative period (anti-infection, pressure, blood volume, alkali, analgesia and the use of glucocorticoids) to improve the patient’s pathophysiological condition and prevent delirium as much as possible are very important, administration of ED is also highly critical to change his prognosis. At present, it has been believed that dexmedetomidine could decline the incidence of delirium, techniques from the case equally prove its effectiveness and analyze benefits in the cardiac in ED.

Dexmedetomidine is an effective highly selective α-2 adrenergic receptor agonist with anti-sympathetic, sedative, amnesia and analgesic properties and is considered a useful and safe adjuvant in many clinical applications. It provides a unique “conscious sedation”, analgesia, and no respiratory inhibition (Bajwa S, Kulshrestha A., 2013). More importantly, it has been characterized by the pharmacokinetics of rapid distribution, short half-life, which means that the effects of age and multiple complications are weak for its metabolism (Dyck JB, Maze M, et al., 1993). Surprisingly. it was assured that dexmedetomidine had anti-inflammatory properties and cut down the need for opioids and benzodiazepines, both of which are probable causes of delirium (Ueki M, Kawasaki T, et al., 2014). Worthy of mention, it has a certain protective action on acute kidney injury in old men (Peng K, Li D, et al., 2019). However, it has been still being explored about its advantages and disadvantages on the heart. The advantages are as follows: Prevent ischemia-reperfusion injury and the arrhythmic. The former can increases coronary artery blood flow, slow heart rate down by prolonging the repolarization and effective refractory period of myocardium (Yoshitomio, Chos, et al., 2021). Dong et al. confirmed that the pretreatment of dexmedetomidine could effectively reduce ischemia reperfusion injury and played a protective role on the heart of aged rats (Dong J, Guo X, et al., 2017). The latter is clearly beneficial in cardiac surgery, which reduces the risk of postoperative ventricular tachycardia, POD, and atrial fibrillation, and shorten total hospital stay (Liu H, JiF, PengF, et al., 2017). In general, the measures preventing atrial fibrillation and adopting dexmedetomidine can decrease myocardial perfusion, inhibit inflammatory response, reduce serum catecholamine levels and enhance the sensitiveness of Vagus Nerve (VN). On the other hand, the inhibitory consequences on the heart are mainly characterized by negative frequency and negative conduction. As the pharmacological action of dexmedetomidine, the activity of vagus nerve exceeds the sympathetic nerves, which is one of the reasons for increasing the tension of central vagus nerve. When potassium channels in cardiac membrane are partially closed, their action potential duration is prolonged and heart rate slows, suggesting that the mechanism of dexmedetomidine inducing bradycardia may be related to K+ outflow (Maldonado JR, Wysong A, et al., 2009). Zhu et al showed that it did not affect the cardiac conduction system, but the load doses of 0.5 and 0.8 ug/kg could effectively shorten the QT interval. Therefore, dexmedetomidine had better not exceed 0.5 ug/kg in patients with slow heartbeat, keeping from severe bradycardia (Shu Zhu, Jia-Min Zhang, et al., 2018).

Reviewing the patient's history, it was found that, upon arriving at PACU, the patient's heart rate (138 times/min) and blood pressure (138/106 mmHg) were high and the regulation ability of circulatory system was decreased due to age, and abdominal infection was severe. Actually, at that time, dexmedetomidine was the best choice for the patient. Unfortunately, we used it after other therapeutic interventions were proven less effective in this case. In addition, it may indicate that the dose regulation (0.5 μg/kg for 15 min, following 0.4μg/kg/h) was desirable. Learning from this case, we reminded that anesthetists can regard dexmedetomidine as a preferable choice when administering patients parallelled with the patient we described. Though it rarely causes severe left ventricular dysfunction and refractory shock, it was extremely necessary for us to cope cautiously with patients suffering from cardiac insufficiency. In a word, circumstances alter cases.

Conclusion

To sum up, we reviewed the delirium-causing various factors, analyzed the causes of ED in patient from this case. It was approved of the therapeutic effect of dexmedetomidine in the elderly during anaesthesia recovery in PACU. Furthermore, it is friendly to patients with heart disease and has no adverse events. Based on the article, we hope health care providers step up vigilance, and don't have any delays in coping with patients exposed to adverse environments with the administration of dexmedetomidine. Of course, we look forward to more samples being collected to persuasively prove that early identification and intervention, such as dexmedetomidine be used in combination with anesthesia induction, especially for high-risk patients with ED, in PACU, which could significantly narrow the risk of ED and adverse events.

Ethical statement

The research was conducted ethically in accordance with the Helsinki Declaration and approved by the Biomedical Research Ethics Committee of the West China Hospital of Sichuan University.

Consent to participate

The patient provided written consent to publish this case.

Conflict of interest

The authors declare that they have no competing interests.

Funding

None.

Transparency statement

The authors affirm that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

Authors’ contributions

Yue Gu collected the clinical data; Hong-Su Zhou and Yi-Huan Guan completed the manuscript. All authors have no conflicts of interest to disclose. All authors have read and approved the final submitted manuscript.