Different doses of dexmedetomidine combined with propofol for older adults undergoing cardiac surgery: the impact on postoperative delirium

Abstract

Objective

This study retrospectively investigated the effects of different doses of dexmedetomidine combined with propofol on postoperative delirium in older adults undergoing cardiac surgery.

Methods

The medical records of 82 older adults undergoing cardiac surgery admitted to two hospitals between August 2019 and August 2022 were analyzed. The participants were divided into two groups based on the dexmedetomidine dose: group A (0.5 µg/kg dexmedetomidine + propofol) and group B (1.0 µg/kg dexmedetomidine + propofol). The mean arterial pressure (MAP), heart rate (HR), anesthesia depth index (NTI), and incidence of postoperative delirium (POD) at 7 days after surgery were compared.

Results

MAP and HR were significantly higher in group A than in group B during extubation and 10 minutes after extubation and significantly higher than the values before anesthesia induction. At all time points post-anesthesia induction, NTI was higher in group B than in group A, and the incidence of POD within 7 days after surgery was significantly higher in group A. The Prince–Henry pain scores were higher in group A than in group B at 1, 4, 24, and 48 hours after surgery.

Conclusions

Higher dexmedetomidine doses were associated with more stable hemodynamics and stronger effects on POD in older adults undergoing cardiac surgery.

Keywords

Cardiac surgery dexmedetomidine older adult postoperative delirium propofol hemodynamics

Introduction

The monitoring and management of hemodynamics, sedation, and analgesia in patients undergoing cardiac surgery are directly related to the success and prognosis of surgery. The cerebral vessels of older adults often exhibit insufficient cerebral perfusion because of atherosclerosis and stenosis, whereas non-pulsatile blood flow during cardiopulmonary bypass further damages cerebral blood circulation, significantly increasing the risk of postoperative delirium (POD) and affecting the surgical outcome.^1,2 Propofol can be used for anesthesia in patients undergoing cardiac surgery; however, it has the disadvantage of disrupting circulation and potentially leads to complications such as hypotension and respiratory depression during induction.^3,4 Dexmedetomidine has the advantages of sedation and analgesia, and it can prevent transient hypertension during anesthesia and stabilize the patient’s blood pressure during skin incision and sternotomy, thereby reducing dependence on other anesthetic drugs. Previous studies found that dexmedetomidine can effectively reduce the incidence of postoperative delirium and rapid arrhythmia and significantly reduce the dosage of anesthesia.^4,5 Therefore, it is crucial to ensure the safety of intravenous anesthetic drugs in older adults undergoing cardiac surgery. Against this backdrop, this study explored the sedative and analgesic effects of dexmedetomidine combined with propofol in older adult cardiac surgery as well as its effects on cognitive function, hemodynamics, and consciousness recovery time. This study aimed to provide a reference for rational medication usage and the prevention of postoperative complications in older adults.

Materials and methods

General information

Retrospective analysis of the medical records and follow-up data of older adults undergoing cardiac surgery admitted to two hospitals from August 2019 to August 2022 was conducted. The study participants were divided into two groups according to the dose of dexmedetomidine: group A (0.5 µg/kg dexmedetomidine + propofol) and group B (1.0 µg/kg dexmedetomidine +propofol). The inclusion criteria were as follows: (1) patients with coronary atherosclerosis, congenital heart disease, or other heart diseases who required surgery; (2) age >60 years; (3) American College of Anesthesiologists grades I to III; and (4) no history of long-term use of sedatives. The exclusion criteria were as follows: (1) patients who experienced continuous postoperative coma, (2) alcohol dependence, (3) history of cognitive impairment, (4) simple intervention therapy, (5) prior thoracoabdominal aortic artificial vessel replacement surgery, (6) mental disorders, (7) use of medication that affects neurological and psychiatric function within 1 month before surgery, and (8) incomplete clinical data. We de-identified all patient details. Written informed consent was also obtained from each patient. We also conducted our study in accordance with the Declaration of Helsinki of 1975, as revised in 2013. The reporting of this study conforms to the STROBE guidelines.⁶ The review board waived the requirement for approval.

Preparation before anesthesia

Before surgery, general conditions such as blood pressure and blood sugar were maintained within a controllable range. Cardiac surgery was performed under extracorporeal circulation, and the patient’s heart function was evaluated to prepare for rescue from intraoperative complications. Simultaneously, any nervousness experienced by the patient was relieved, and, when necessary, sedatives were administered to avoid stress. Before starting anesthesia, the airtightness of important respiratory pipelines was checked, and the anesthesia machine was assessed for its ability to operate normally. After the patient entered the operating room, the ambient temperature was maintained at 21 to 25°C, and heating measures were actively provided for patients experiencing hypothermia. After verifying the patient’s general condition, electrocardiography and blood pressure monitoring were performed. The left arm was connected to a neuromuscular monitoring device to monitor muscle relaxation, and the relevant instruments for tracheal intubation were prepared to ensure that there was no air leakage from the airbag. The tracheal catheter was lubricated after shaping.

Anesthesia induction

Owing to long-term fasting, the influence of drugs such as propofol during surgery, and poor compensatory ability, older adults are prone to hypotension and other conditions. The following measures can reduce the occurrence of such reactions: preoperative fluid replacement, selection of anesthetic drugs to stabilize blood pressure, appropriate administration of vasoactive drugs during the induction period to maintain blood pressure stability, and pre-administration of midazolam 0.50 mg/kg intravenous injection to reduce tension and anxiety. Etomidate 0.3 mg/kg was used at the beginning of extracorporeal circulation, with minimal impact on circulation, and cisatracurium 0.2 mg/kg was used for muscle relaxation. Because of the high irritancy of the double lumen catheter, intravenous sufentanil 0.5 µg/kg was used for analgesia to avoid excessive stimulation in patients. Subsequently, tracheal intubation was performed, and vital signs were monitored to prevent bradycardia after the laryngoscope had lifted the epiglottis. After the glottis was opened, a pen-style technique was used to insert the tracheal tube to the appropriate depth. The tube was inflated with a syringe, anesthesia was activated to control breathing, and the waveform of end-tidal carbon dioxide was monitored to confirm successful intubation. Under normal ventilation, the tidal volume was set to 6 to 8 mL/kg, the respiratory rate was set to 10 to 12 times/minute, and the inhalation-to-exhalation ratio was 1:2.

Anesthesia maintenance

During the surgery, patients in group A received 0.5 µg/kg dexmedetomidine for 10 minutes, followed by a continuous infusion of propofol at a rate of 4 to 6 mg/kg/hour, with an additional 50 to 100 µg of sufentanil provided depending on the situation. Patients in group B received 1 µg/kg dexmedetomidine during surgery for 10 minutes, followed by the same infusion of propofol and sufentanil as administered in group A. When hypotension occurred, norepinephrine was used to regulate blood pressure. When the heart rate slowed to 40 beats per minute or less, atropine was administered. After the termination of extracorporeal circulation, reversal was achieved using 1 mg of protamine per 100 U of heparin.

Postoperative management

The level of anesthesia was slowly reduced before the end of the surgery, the depth of sedation was reduced, and the patient was assessed to determine whether his or her cardiovascular function could tolerate extubation. Owing to the relative increase in the circulating blood volume after the patient awakens, the cardiovascular burden on older adult patients increases and needs to be taken seriously. In both groups of patients, the drug infusion was stopped 5 minutes before surgery, and patients were assessed for muscle relaxation before extubation. After extubation, muscle relaxation can be monitored, and a value <0.9 indicates the presence of residual blocking effects of muscle relaxants. After confirming the absence of residual muscle relaxants, the patients were transferred to the ICU for further monitoring. After surgery, a wireless electronic analgesic pump administered sufentanil (1.5 µg/kg) in combination with 15 mg of dexamethasone and 150 mL of physiological saline. The parameters of the analgesic pump were set to an initial dose of 2 mL, a single dose of 1.5 mL, and a background dose of 2 mL/hour, and the time was set to 15 minutes.

Observation indicators

Before anesthesia induction (T0), at the beginning of surgery (T1), at the end of surgery (T2), at the time of extubation (T3), and 10 minutes after extubation (T4), each patient’s mean arterial pressure (MAP), heart rate (HR), and anesthesia depth index (NTI) on the multifunctional electrocardiogram monitor were observed and recorded. After the completion of intravenous drug infusion, the start of spontaneous breathing, eye opening, extubation, and verbal statement of the two groups were timed, the difference was calculated, and the time used was recorded. The Prince–Henry pain score was determined according to the patient’s reported pain sensation at 1 , 4, 24, and 48 hours after surgery.⁷ The total score ranged 0 to 4, with 0 indicating no pain, 1 indicating pain during coughing, 2 indicating pain during deep breathing, 3 indicating tolerable pain at rest, and 4 indicating unbearable pain at rest. The delirium assessment method was used to evaluate the cognitive status of patients every day within 7 days after surgery, and the incidence of delirium was calculated. The delirium assessment criteria were as follows: a, sudden onset with repeated fluctuations in the condition; b, disordered thinking and disorderly speech; c, decreased attention and mental confusion; and d, consciousness disorder characterized by a decrease in the clarity of perception of the environment, which can range from mild blurring of consciousness to coma with significant changes in circadian rhythms. Delirium can be diagnosed when any one of a, b, c, or d appears. A sample of 4 mL of fasting venous blood was collected from patients before anesthesia induction, as well as at 12, 24, and 48 hours after surgery. ELISA was used to detect the serum concentrations of S-100β, IL-1β, IL-6, and TNF-α in patients.

Statistical methods

IBM SPSS 23.0 (IBM Corp., Armonk, NY, USA) was used for data analysis. Measurement data that followed a normal distribution were summarized as the mean ± standard deviation, whereas the counting data were summarized as rates. Continuous variables were compared using the t-test. Non-parametric tests were used to analyze data with non-normal distributions, and intergroup comparisons were performed using the chi-square test. Statistical significance was set at P < 0.05.

Results

Comparison of indicators, pain scores, and consciousness recovery time between two groups

The study cohort consisted of 82 older adults with an average age of 66.18 ± 4.13 years. Group A included 22 men and 18 women with an average age of 66.44 ± 4.03 years, whereas group B included 18 men and 24 women with an average age of 65.01 ± 4.28 years. Comparison of the baseline data of the two groups revealed no statistically significant differences in age, sex, types of surgery, extracorporeal circulation, and cross-clamping time (all P > 0.05). At T0, T1, and T2, there were no significant differences in MAP or HR between the two groups. However, at T3 and T4, MAP and HR were significantly higher in group A than in group B, and the values were higher at these times than at T0 (all P < 0.05). At T1 to T4, NTI was greater in group B than in group A (P < 0.05, Table 1). Eight and two cases of POD occurred in groups A (n = 40) and B (n = 42), respectively, within 7 days after surgery. The incidence in group A reached 20%, compared with 4.76% in group B (P < 0.05). The Prince–Henry pain scores at 1, 4, 24, and 48 hours postoperatively were higher in group A than in group B (all P < 0.05, Table 2). There was no statistically significant difference in the time of recovery of spontaneous respiration between the two groups (P > 0.05). Group A had longer eye-opening, extubation, and speech statement times than group B (all P < 0.05, Table 3).

Table 1.

MAP, HR, and NTI at T1–T4 for the two groups (n = 82).

Category	Group	T0	T1	T2	T3	T4
MAP (mmHg)	Group A	74.5 ± 10.1	71.5 ± 12.2	73.6 ± 11.8	90.8 ± 12.6^a	88.4 ± 10.5^a
MAP (mmHg)	Group B	75.2 ± 10.5	75.5 ± 12.6	75.9 ± 11.0	75.1 ± 13.6^b	71.5 ± 10.4^b
HR (times/minute)	Group A	73.0 ± 6.1	66.8 ± 5.9	68.5 ± 9.2	88.2 ± 7.6^a	82.1 ± 6.8^a
HR (times/minute)	Group B	71.5 ± 9.2	68.7 ± 7.2	70.1 ± 8.6	73.0 ± 5.9^b	70.1 ± 5.9^b
NTI	Group A	97.5 ± 1.8	35.8 ± 11.0^a	45.0 ± 9.8^a	49.0 ± 8.1^a	64.8 ± 8.0^a
NTI	Group B	98.0 ± 1.9	52.8 ± 9.1^ab	58.6 ± 7.9^ab	64.6 ± 5.7^ab	78.9 ± 4.8^ab

Note: ^aIntragroup comparison, compared with T0, P < 0.05; ^bIntergroup comparison, compared with group A, P < 0.05.

MAP, mean arterial pressure; HR, heart rate; NTI, anesthesia depth index; T0, before anesthesia induction; T!, at the beginning of surgery; T2, at the end of surgery; T3, at the time of extubation; T4, 10 minutes after extubation (T4),

Table 2.

Price–Henry pain scores postoperatively in the two groups (n = 82).

Group	n	1 hour after surgery	4 hours after surgery	24 hours after surgery	48 hours after surgery
Group A	40	3.20 ± 0.28	3.24 ± 0.28	2.90 ± 0.18	2.19 ± 0.15
Group B	42	2.18 ± 0.15	2.21 ± 0.18	1.82 ± 0.15	1.58 ± 0.18
t		20.699	19.911	29.572	16.628
P		<0.001	<0.001	<0.001	<0.001

Table 3.

Recovery time of consciousness after anesthesia cessation in the two groups (n = 82).

Group	n	Autonomous breathing recovery time (minutes)	Eye-opening time (minutes)	Extubation time (minutes)	Speech statement time (minutes)
Group A	40	2.18 ± 0.58	2.48 ± 1.01	3.89 ± 1.52	5.99 ± 1.89
Group B	42	1.97 ± 0.62	1.99 ± 0.58	2.52 ± 0.85	4.60 ± 1.52
t		1.582	2.677	5.069	3.678
P		0.117	<0.001	<0.001	<0.001

Comparison of serum S-100β, IL-1β, IL-6, and TNF-α concentrations between the two groups at different time points

Before anesthesia induction, there were no significant differences in the serum concentrations of S-100β, IL-1β, IL-6, and TNF-α between the two groups (all P > 0.05). However, compared with the values before anesthesia induction, the concentrations of S-100β, IL-1β, IL-6, and TNF-α increased at 12, 24, and 48 hours after surgery in both groups. In addition, the concentrations of S-100β, IL-1β, IL-6, and TNF-α at 12, 24, and 48 hours after surgery were significantly lower in group B than in group A (all P < 0.05, Table 4).

Table 4.

Concentrations of S-100β, IL-1β, IL-6, and TNF-α at different postoperative time periods in the two groups (n = 82).

Category	Group	Before anesthesia induction	12 hours after surgery	24 hours after surgery	48 hours after surgery
S-100β (μg/L)	Group A	0.27 ± 0.06	0.48 ± 0.13*	0.96 ± 0.18*	0.35 ± 0.09*
S-100β (μg/L)	Group B	0.26 ± 0.08	0.35 ± 0.10*^▲	0.37 ± 0.10*^▲	0.26 ± 0.08^▲
IL-1β (pg/L)	Group A	17.75 ± 2.62	28.72 ± 3.41*	45.72 ± 6.68*	31.92 ± 4.25*
IL-1β (pg/L)	Group B	18.76 ± 2.72	20.65 ± 4.85*^▲	33.10 ± 5.20*^▲	19.76 ± 2.60^▲
IL-6 (pg/L)	Group A	21.08 ± 3.10	38.15 ± 5.66*	41.38 ± 6.79*	37.65 ± 5.42*
IL-6 (pg/L)	Group B	21.11 ± 3.15	24.09 ± 3.95*^▲	28.19 ± 4.41*^▲	21.10 ± 3.38*^▲
TNF-α (pg/L)	Group A	27.18 ± 4.10	44.36 ± 7.10*	50.82 ± 8.48*	44.39 ± 7.62*
TNF-α (pg/L)	Group B	28.52 ± 4.10	35.08 ± 5.71*^▲	37.19 ± 6.02*^▲	27.39 ± 5.18*^▲

Note: *Intragroup comparison, compared with before anesthesia induction, P < 0.05; ^▲Intergroup comparison, compared with group A, P < 0.05.

Discussion

POD is a surgical complication that is more common in older adults. Prior studies reported that older patients have poor tolerance to surgery.⁸ Diseases such as brain atrophy can increase the risk of POD; therefore, the timely prevention of delirium is key to ensuring a good postoperative prognosis. Propofol has adverse effects such as respiratory depression and hypotension, making it crucial to identify a novel intravenous anesthetic that is safe and effective.⁹ Alpha-2 adrenergic receptor agonists might act on the alpha-2 receptors in the locus coeruleus of the brainstem, thereby stimulating the sympathetic nervous system and exerting sedative and calming effects.¹⁰ The alpha-2 receptors in the locus coeruleus of the brainstem might cause an increase in potassium ion concentrations in the dorsal horn, leading to target cell hyperpolarization, reduced excitability, and analgesic effects. Dexmedetomidine is an alpha-2 adrenergic receptor agonist with strong anti-sympathetic effects that can reduce the incidence of elevated blood pressure during tracheal intubation.^11,12 However, there is limited research on the optimal dosage of this drug, and it is necessary to explore its impact on anesthesia efficacy and postoperative complications.

This study demonstrated that the incidence of POD within 7 days after surgery was significantly higher in group A than in group B (P < 0.05), indicating that anesthesia with dexmedetomidine (1.0 µg/kg) can help prevent POD in older adults undergoing cardiac surgery. Dexmedetomidine has high affinity for binding to alpha-2 receptors, and it can effectively inhibit respiratory complications, prevent intraoperative hypoxemia, and improve cerebral blood flow perfusion while ensuring its sedative and analgesic functions. In addition, the drug can protect neurons. Researchers confirmed that dexmedetomidine can reduce the secretion of catecholamines in children, reduce stress, and protect brain tissue. High concentrations of dexmedetomidine can maximize its protective effect on the brain tissue while ensuring its safety. Our study found that MAP and HR in group A were significantly higher at T3 and T4 than at T0 (P < 0.05). At T3 and T4, MAP and HR were significantly higher in group A than in group B, indicating that 1.0 µg/kg dexmedetomidine can alleviate hemodynamic fluctuations and control arterial pressure levels to the greatest extent possible. During both the anesthesia maintenance and recovery periods, patients recorded a milder stress response after receiving dexmedetomidine. Therefore, dexmedetomidine (1.0 µg/kg) can stabilize hemodynamics, and its efficacy is dose-dependent.

Postoperative pain is a risk factor for delirium, and the degree of pain is positively correlated with the incidence of POD.^13,14 This study found that group A had higher Prince–Henry pain scores than group B at 1, 4, 24, and 48 hours after surgery (P < 0.05). This indicates that 1.0 µg/kg dexmedetomidine is beneficial for postoperative pain management, and it promotes postoperative recovery in patients undergoing cardiac surgery. However, low doses might not achieve optimal results, as the effective blood drug concentration is low and its therapeutic effect is limited. In addition, group A had longer eye-opening, extubation, and speech presentation times than group B (P < 0.05). Dexmedetomidine belongs to the sedative class of drugs, and it has a small impact on respiration, mainly affecting the performance of motor commands. Therefore, the dosage of dexmedetomidine is generally not linearly related to indicators such as eye-opening, extubation, and speech statement times. The specific effect of the dexmedetomidine dosage on the duration of extubation should be investigated in further research, but lower doses might not be associated with better outcomes. Furthermore, research indicated that during cardiac surgery, a large number of inflammatory factors are released because of reperfusion injury, and damage to cells is caused by extracorporeal circulation, further exacerbating brain damage.

Conclusion

This study confirmed that dexmedetomidine (1.0 µg/kg) can significantly inhibit the release of cytokines, achieve significant anti-inflammatory effects, protect brain cells, and reduce the incidence of delirium. It also has a good safety profile. In summary, the combination of dexmedetomidine and propofol can effectively prevent POD in older adults after cardiac surgery. A dexmedetomidine dose of 1.0 µg/kg of is safer, and it results in a lower incidence of delirium.

Footnotes

Authors’ contributions

HW and HH contributed to the drafting of the manuscript and design of the study. YFL and JXY contributed substantially to the conceptualization and design of the study. JXY and YFL confirm the authenticity of the raw data. All authors read and approved the final manuscript.

Data availability statement

All data generated or analyzed during this study are included in this published article.

Declaration of conflicting interests

The authors declare that they have no competing interests.

Funding

This study was funded by grants from the Hexi University 14th Science and Technology Innovation Project (No. 164).

ORCID iD

Jiaxi Yao

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