Effects of dexmedetomidine on cerebral oxygen saturation and postoperative cognitive function in elderly patients undergoing minimally invasive coronary artery bypass surgery

Abstract

OBJECTIVE:

This study aimed to investigate the effects of dexmedetomidine on cerebral oxygen saturation [Sct(O₂)] and postoperative cognitive function in elderly patients undergoing minimally invasive coronary artery bypass graft surgery.

METHODS:

Sixty elderly patients who received minimally invasive coronary artery bypass graft surgery were randomly equally divided into dexmedetomidine group (group D) and control group (group N). The patients in group D were pumped with 1 μg/kg dexmedetomidine for 15 min before incision, followed by continuous pumping at 0.3–0.5 μg/(kg·h) till the end of the operation. The patients in group N received same dose of normal saline during the operation. Sct(O₂) was monitored at pre-induction (T0), post-induction (T1), 30 min (T2) after single-lung ventilation, and after surgery (T3). Mini-mental state examination (MMSE) was used to assess the cognitive function at 1 day before, 72 hour and 7 days after surgery.

RESULTS:

Sct(O₂) level in group D was significantly higher than that in group N at T2 (P < 0.05). Sct(O₂) level was statistically lower at T2 than that at T0, T1 and T3 in the same group N (P < 0.05). At 72 h and 7d after operation, the incidence of cognitive dysfunction in group D was markedly lower than that in group N (P < 0.05), the MMSE score in group D was markedly higher than those in group N, but was significantly lower than that before surgery (P < 0.05).

CONCLUSION:

Dexmedetomidine can alleviate the decrease of Sct(O₂) during single-lung ventilation, improve postoperative cognitive function, and reduce the incidence of POCD in elderly patients with minimally invasive coronary artery bypass surgery.

Keywords

Dexmedetomidine minimally invasive coronary artery bypass surgery elderly cognitive dysfunction

1 Introduction

Postoperative cognitive dysfunction (POCD) broadly refers to deterioration in cognition temporally associated with surgery and occurs after anesthesia, mainly manifested as mental confusion, personality changes, memory loss, mental disorders, and social impairment. It may cause loss of self-care ability and Alzheimer’s disease in severe case [1]. POCD represents neurological complications due to cardiac surgery and leads to a morbidity of 30–79% [2]. The actual incidence of POCD depends on the types of operation, and it is more pronounced in patients receiving a cardiac operation than in those undergoing a non-cardiac operation [3]. The spectrum of cognition abilities is diverse, including learning and memory, verbal abilities, perception, attention, executive functions, and abstract thinking. Therefore, POCD is typically diagnosed using neuropsychological clinical tests, including the logical memory test, the test of CERAD word list memory, the Boston naming test, category fluency test, digit span test, trail making test, and digit symbol substitution test [4]. Moreover, serum biomarkers are also applied to aid the diagnosis, such as S100β and neuron-specific enolase (NSE) [5].

Dexmedetomidine (Dex) is a highly selective α2 receptor agonist with sedative, analgesic, anti-inflammatory effects. Dex contributes to attenuating excessive inflammatory responses in neurons, and thereby properly preventing the development of POCD [6]. The study with Dex treatment revealed that the neuronal apoptosis was markedly reduced via over-expression of relaxin-3 and decrease of cytokines such as IL-1beta, IL-6 and Dex can restore neurogenesis and plasticity in hyperoxia-induced injury [7, 8]. A recent finding based on clinical data of 58 patients with ischemic cerebrovascular disease showed that their postoperative cognitive dysfunction and attention network function were evidently improved by the Dex therapy [9].

Minimally invasive coronary artery bypass surgery requires single-lung ventilation, which may decrease cerebral oxygen saturation and affect postoperative cognitive function [10]. It allows adequate exposure, multi-vessel coronary surgical precision, and complete revascularization from a small thoracotomy incision, often without cardiopulmonary bypass, which may cause complications such as bleeding requiring transfusion, stroke, acute kidney injury, atrial fibrillation, infection, a slow return to full physical activity. By avoiding sternotomy, patients who receive minimally invasive coronary artery bypass surgery recover significantly faster in the early postoperative period [11]. However, this type of surgery may still give rise to certain tissue trauma, myocardial and neurological damage [12]. The aim of this study was to investigate the effects of dexmedetomidine on cerebral oxygen saturation and postoperative cognitive function in elderly patients undergoing minimally invasive coronary artery bypass graft surgery.

2 Materials and methods

2.1 General information

Sixty patients received minimally invasive off-pump coronary artery bypass grafting (OPCABG) were enrolled with the age of 65 to 75 years old and the body weight of 55 to 85 kg. Inclusion criteria: ASA II or III, NYHA grade II or III, no previous acute myocardial infarction, no previous diagnosis of heart failure, no diabetes, no brain trauma, no cerebrovascular accident, or no mental illness, and left ventricular ejection fraction >40%. Exclusion criteria: abnormal liver and kidney function, sedatives or antidepressants intake, history of drug abuse, or accompanied by sick sinus syndrome. Patients were randomly and equally divided into Dex group (group D) and normal saline group (group N), 30 cases in each group. This study was approved by the Medical Ethics Committee of the hospital. All patients had signed informed consent.

2.2 Method

The patients were routinely required preoperative fasting for 8 hours before surgery. NIBP, ECG and SPO2 were continuously monitored. The Sct(O₂) was tested by a cerebral oxygen saturation monitor, and the average value of Sct(O₂) on both sides was taken. All patients had bilateral NEAR infrared-reflected spectroscopy (NIRS) probes applied to the forehead before the induction of anesthesia in order to monitor cerebral oxygen saturation. NIRS values were obtained from the patients while breathing room air as well as on supplemental oxygen (4 l/min O₂ via nasal prongs). The rSO₂ values with supplemental oxygen were used as the baseline values for the study. The left iliac artery was punctured under the local anesthesia to monitor arterial blood pressure. Anesthesia induction: midazolam 0.08 mg/kg, sufentanil 1.0–1.5 μg/kg, etomidate 0.3 mg/kg, and cis-atracurium 0.4 mg/kg. After induction, double lumen endobronchial intubation was performed. The tidal volume VT = 7∼8 mL/kg, respiratory frequency RR = 10∼12 times/min, and respiratory ratio I:E = 1 : 2. During single lung ventilation, V_T = 6 mL/kg, RR = 12∼16 times/min, other ventilation parameters were unchanged, and PETCO2 was maintained at 35∼45 mmHg. A four-chamber central venous catheter was inserted into the right internal jugular vein for infusion, monitoring CVP, and pumping vasoactive drugs. Anesthesia was maintained with propofol 4–6 mg/(kg·h) and sufentanil 0.8–1 μg/(kg·h) for continuous infusion. According to the duration of the operation, 10 mg cis atracurium was intermittent intravenous injected to maintain BIS at 40 ∼ 60. Patients in group D were pumped with a loading dose of 1 μg/kg Dex at 15 min before the incision, followed by continuous pumping at the rate of 0.3–0.5 μg/(kg·h) till the end of the operation. The patients in group N were given the same dose of 0.9% saline. During the operation, sodium lactate Ringer’s solution, voluven, and autologous blood were infused according to the condition. Vasoactive drugs were used to maintain circulation stability when necessary. At the end of the operation, the pumping of the anesthetic was stopped and the tracheal tube was taken to the ICU ward. At an intervention threshold of a 10% decrease in rSO₂ value relative to baseline for a duration exceeding 15 s, anesthesiologists used an interventional algorithm to reverse desaturations. The 10% threshold level was chosen so as to intervene as early as possible to maintain rSO₂ at baseline values throughout the surgery and avoid an a priori defined clinically significant decreases in rSO₂ value below 20% relative to baseline. Every desaturation occurrence along with its intervention (success or failure) was noted as previously reported [13]. After the patient was awake, an analgesic pump (sufentanil 100 μg + tropisetron 4 mg + normal saline 100 ml) was injected at 2 ml/h with locking time at 15 minutes to sustain analgesia for 48 hours.

2.3 Observation index

Sct(O₂) was monitored at pre-induction (T0), post-induction (T1), 30 min (T2) after single-lung ventilation, and after surgery (T3). Mini-mental state examination (MMSE) was used to assess the cognitive function at 1 day before, 72 hour and 7 days after surgery.

The American Psychiatric Association’s POCD diagnostic criteria: 1. A decrease in awareness to the environment, and a decrease in attention to shift concentration and maintain environmental stimuli. 2, at least two of the following: a, perceptual disorder; b, language incoherence; c, sleep awake rhythm loss; d, increased or decreased neuromotor activity. 3. directional disorders and memory loss. 4, clinical performance sustained for several hours or even days. 5. History of surgical anesthesia.

2.4 Statistical analysis

All data analyses were performed on SPSS16.0 software. The normal distributed measurement data were expressed as mean±standard deviation (±s). t test was used for the comparison between two groups, and chi-square test was used for enumeration data. Continuous data from multiple groups were analyzed by using one-way ANOVA, with the Tukey’s post hoc test. P < 0.05 was considered as statistical significance.

3 Results

3.1 General condition comparison

There was no statistical difference observed between general condition, the operation time, and the number of bypass grafts between the two groups (P > 0.05) (Table 1).

Table 1
Comparison of general information, intraoperative vasoactive drugs used and hemodynamic changes, analgesia

Group

D N

Male/female (cases) 14/16 15/15

Age(year, $\bar{x} \pm s$ ) 69.5±5.1 70.4±4.2

Height(cm, $\bar{x} \pm s$ ) 165.6±7.2 164.5±6.4

Weight (kg, $\bar{x} \pm s$ ) 65.5±11.2 64.6±9.3

ASA grade (II/III, case) 11/19 10/20

Operation duration (min, $\bar{x} \pm s$ ) 240.8±48.7 230.9±54.6

The number of bypass grafts 1 1

Norepinephrine (μg, $\bar{x} \pm s$ ) 20.5±5.1 20.4±4.3

Dopamine (μg, $\bar{x} \pm s$ ) 65.6±6.2 64.7±6.4

Nitroglycerin (μg, $\bar{x} \pm s$ ) 65.5±11.2 64.6±9.3

Phenylephrine (μg, $\bar{x} \pm s$ ) 130.8±26.7 130.9±24.6

Bypass begin (MAP) (mmHg, $\bar{x} \pm s$ ) 90.2±12.3 91.3±13.5

Bypass 10min (MAP) (mmHg, $\bar{x} \pm s$ ) 85.6±16.5 86.8±15.6

Sufentanil (μg, $\bar{x} \pm s$ ) 310.5±70.1 300.4±80.3

Midazolam (μg, $\bar{x} \pm s$ ) 5.8±0.2 6.2±0.4

Intraoperative bleeding (ml, $\bar{x} \pm s$ ) 350.5±89.2 354.6±92.3

Postoperative sufentanil (μg, $\bar{x} \pm s$ ) 130.5±26.4 132.5±28.3

Decrease of heart rates (beats/min, $\bar{x} \pm s$ ) 17±5^**** 1±4

	Group
Male/female (cases)	14/16	15/15
Age(year, $\bar{x} \pm s$ )	69.5±5.1	70.4±4.2
Height(cm, $\bar{x} \pm s$ )	165.6±7.2	164.5±6.4
Weight (kg, $\bar{x} \pm s$ )	65.5±11.2	64.6±9.3
ASA grade (II/III, case)	11/19	10/20
Operation duration (min, $\bar{x} \pm s$ )	240.8±48.7	230.9±54.6
The number of bypass grafts	1	1
Norepinephrine (μg, $\bar{x} \pm s$ )	20.5±5.1	20.4±4.3
Dopamine (μg, $\bar{x} \pm s$ )	65.6±6.2	64.7±6.4
Nitroglycerin (μg, $\bar{x} \pm s$ )	65.5±11.2	64.6±9.3
Phenylephrine (μg, $\bar{x} \pm s$ )	130.8±26.7	130.9±24.6
Bypass begin (MAP) (mmHg, $\bar{x} \pm s$ )	90.2±12.3	91.3±13.5
Bypass 10min (MAP) (mmHg, $\bar{x} \pm s$ )	85.6±16.5	86.8±15.6
Sufentanil (μg, $\bar{x} \pm s$ )	310.5±70.1	300.4±80.3
Midazolam (μg, $\bar{x} \pm s$ )	5.8±0.2	6.2±0.4
Intraoperative bleeding (ml, $\bar{x} \pm s$ )	350.5±89.2	354.6±92.3
Postoperative sufentanil (μg, $\bar{x} \pm s$ )	130.5±26.4	132.5±28.3
Decrease of heart rates (beats/min, $\bar{x} \pm s$ )	17±5^****	1±4

^**** P < 0.0001, compared with group N.

3.2 Intraoperative vasoactive drugs used and hemodynamic changes comparison

There was no significant difference in the dose of norepinephrine, dopamine, nitroglycerin, and phenylephrine, and hemodynamic changes between the two groups (P > 0.05). Notably, during the loading dose, the patient’s heart rate decreased significantly compared to group N (P < 0.0001). Within 1 hr of discontinuation of the dexmedetomidine infusion, the baseline heart rate had recovered, and no further episodes of acute bradycardia were noted (Table 1).

3.3 Analgesia comparison

There was no statistical difference in anesthetic, intraoperative bleeding, and postoperative analgesia between the two groups (P > 0.05) (Table 1).

3.4 Sct(O₂) comparison

Sct(O₂) level in group D was slightly lower than in group N at T0 and T1, but was markedly higher at T2 (Table 2).

Table 2
Comparison of Sct(O₂), MMSE, POCD

Group

D N

Sct(O₂) T₀ (%, $\bar{x} \pm s$ ) 70±3.2^* 72±3.1

T₁ (%, $\bar{x} \pm s$ ) 68±3.3^* 70±3.4

T₂ (%, $\bar{x} \pm s$ ) 65±3.1^** 50±2.3b

T₃ (%, $\bar{x} \pm s$ ) 67±3.2 66±3.3

F 12.69 320.2

R² 0.2471 0.8923

P value <0.0001 <0.0001

MMSE 1d after operation (score, $\bar{x} \pm s$ ) 28.4±1.2 28.2±1.1

3d after operation (score, $\bar{x} \pm s$ ) 24.5±1.1^ 20.3±1.3

7d after operation (score, $\bar{x} \pm s$ ) 28.2±1.3^ 24.2±1.2

F 100 323.6

R² 0.6969 0.8815

P value <0.0001 <0.0001

POCD 3d after operation (%) 10^* 30

7d after operation (%) 0^**** 16.7

		Group
Sct(O₂)	T₀ (%, $\bar{x} \pm s$ )	70±3.2^*	72±3.1
	T₁ (%, $\bar{x} \pm s$ )	68±3.3^*	70±3.4
	T₂ (%, $\bar{x} \pm s$ )	65±3.1^****	50±2.3b
	T₃ (%, $\bar{x} \pm s$ )	67±3.2	66±3.3
	F	12.69	320.2
	R²	0.2471	0.8923
	P value	<0.0001	<0.0001
MMSE	1d after operation (score, $\bar{x} \pm s$ )	28.4±1.2	28.2±1.1
	3d after operation (score, $\bar{x} \pm s$ )	24.5±1.1^****	20.3±1.3
	7d after operation (score, $\bar{x} \pm s$ )	28.2±1.3^****	24.2±1.2
	F	100	323.6
	R²	0.6969	0.8815
	P value	<0.0001	<0.0001
POCD	3d after operation (%)	10^***	30
	7d after operation (%)	0^****	16.7

^*P < 0.05, ^***P < 0.001, ^****P < 0.0001, compared with group N.

3.5 MMSE comparison

At 3d and 7d after operation, the MMSE score in group D was markedly higher than those in group N (P < 0.0001). Of note, the MMSE score at 3d after operation was apparently lower than that at 1d, 7d before surgery in group D (P < 0.05). (Table 2).

3.6 POCD comparison

At 3d and 7d after operation, the incidence of POCD in group D was markedly lower than that in group N (P < 0.0001) (Table 2).

4 Discussion

POCD is closely related to age, surgical procedure, anesthesia time, intraoperative hypoxia, anesthetic drugs, and other factors. It was reported that the incidence of cognitive dysfunction after senile cardiac surgery is 29% to 37% [14]. At present, minimally invasive coronary artery bypass surgery has been widely performed for coronary artery disease [12]. However, since this procedure cannot move the heart, it is only suitable for the anterior descending branch and the diagonal branch. In this study, all the 60 patients received the anterior descending coronary artery bypass. Sct(O2) can visually reflect the oxygenation state of brain tissue. Continuous Sct(O₂) monitoring during operation can detect the changes of cerebral blood flow and the balance of oxygen supply and demand in brain tissue. It was suggested that most single-lung ventilation patients are prone to Sct (O₂) reduction during surgery, which is closely related to the occurrence of POCD [15]. Minimally invasive coronary bypass surgery required single-lung ventilation to complete the procedure [16], which allows us to explore the relationship between cognitive dysfunction and cerebral oxygen saturation after minimally invasive coronary artery bypass surgery.

Dex is a highly selective α2 adrenal receptor agonist [17]. It has been proposed that Dex beneficially influences postoperative cognitive status through an improvement of brain oxygen supply, along with other mechanisms of brain protection, as suggested by animal experiments and clinical studies [18 –20]. However, Clinical studies indicated restriction on the occurrence of sputum by Dex, suggesting a further advantage in elderly critical patients [21]. Dex contributes to neuroprotective effects through animal experiments and clinical studies indicated its restriction on the occurrence of sputum, suggesting a potential therapy for elderly critical patients [8 , 23]. Consistently, our results showed that in group D Sct(O2) was less decreased during single-lung ventilation in comparison with group N. In addition, the incidence of cognitive dysfunction decreased markedly in 72 h and 7d after surgery, indicating that Dex may improve the occurrence of POCD through elevating Sct(O2). Previous finding revealed that, during unilateral ventilation, Dex activated the adrenergic receptors in the pulmonary capillaries, leading to capillary contraction in the lung, an increase in hypoxic pulmonary vasoconstriction (HPV), and a slowing of the intrapulmonary shunt rate (Qs/Qt) [24]. Various factors affect the changes of Sct(O₂) during the single lung ventilation, including cerebral perfusion pressure, Qs/Qt, and so on. Decreased Qs/Qt and elevated Sct(O2) enhanced brain oxygen supply increased and reduced the incidence of POCD.

MMSE is a recommended POCD screening scale. It is evaluated from the aspects of orientation, attention, memory and calculation ability, and memory ability and language ability, thus can reflect the cognitive function status of patients [25]. Our results demonstrated that compared with group N, the MMSE was significantly increased in group D at 72 h and 7d after operation. Our data present that the cognitive function of the control group was significantly lower than that before surgery, and was improved at 7 days after surgery, while Dex apparently improved the cognitive function at 72 h and 7d after surgery. Dex exhibited a good preventive effect on the occurrence of POCD in elderly patients.

5 Conclusion

To sum up, Dex can alleviate the decrease of Sct(O₂) during single-lung ventilation, improve postoperative cognitive function, and reduce the incidence of POCD in elderly patients with minimally invasive coronary artery bypass surgery, which provides new insights for the improvement of minimally invasive coronary artery bypass surgery.

Conflict of interest

None.

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Effects of dexmedetomidine on cerebral oxygen saturation and postoperative cognitive function in elderly patients undergoing minimally invasive coronary artery bypass surgery

Abstract

OBJECTIVE:

METHODS:

RESULTS:

CONCLUSION:

Keywords

1 Introduction

2 Materials and methods

2.1 General information

2.2 Method

2.3 Observation index

2.4 Statistical analysis

3 Results

3.1 General condition comparison

3.3 Analgesia comparison

3.4 Sct(O2) comparison

3.6 POCD comparison

4 Discussion

5 Conclusion

Conflict of interest

References

3.4 Sct(O₂) comparison