Efficacy and safety of different doses of dexmedetomidine on gastrointestinal function recovery after laparoscopic colorectal surgery

Abstract

BACKGROUND

Postoperative gastrointestinal recovery affects hospital stay time and patient’s quality of life. Studies suggest that the use of dexmedetomidine during the perioperative period can promote post operational recovery of gastrointestinal function.

AIM

To evaluate the efficacy and safety of different doses of dexmedetomidine on postoperative gastrointestinal function recovery after laparoscopic colorectal surgery.

METHODS

In this large-sample, retrospective study, 879 patients undergoing laparoscopic colorectal surgery were categorized into three groups: A control group receiving no dexmedetomidine (n = 281), a low-dose group receiving an intraoperative bolus of 0.5 μg/kg dexmedetomidine followed by a continuous infusion of 0.2 μg/kg/hour (n = 313), and a high-dose group receiving a 1.0 μg/kg bolus followed by a 0.5 μg/kg/hour infusion (n = 285). Time to postoperative first flatus, feces, and regular diet, and the intake, feeling nauseated, emesis, physical examination, and duration of symptoms score were evaluated.

RESULTS

Multiple linear regression analysis showed that age, gender, body mass index, American Society of Anesthesiologists classification, comorbidities and surgical site were not related to the time to first flatus (all P > 0.05). The times to postoperative first flatus, first feces, and regular diet were earlier in both dexmedetomidine groups than the control group (both P < 0.05). More patients in the control group experienced postoperative gastrointestinal intolerance (both P < 0.05). There was no significant difference between the high- and the low-dose groups (P > 0.05). The incidence of intraoperative bradycardia in the high-dose group was higher than that in the control group (19.15% vs 8.19%, P < 0.05).

CONCLUSION

Both low- and high-dose dexmedetomidine regimens enhance postoperative gastrointestinal recovery after laparoscopic colorectal surgery. The low-dose regimen demonstrates superior safety, supporting its integration into multimodal enhanced recovery pathways.

Key Words: Dexmedetomidine; Laparoscopic colorectal surgery; Gastrointestinal function; Adverse event; Retrospective study

Core Tip: Both low-dose and high-dose dexmedetomidine enhance gastrointestinal recovery after laparoscopic colorectal surgery, significantly shortening time to first flatus, defecation, and oral intake vs controls. No dose-dependent benefit observed: High-dose dexmedetomidine (1.0 μg/kg + 0.5 μg/kg/hour) did not further accelerate gastrointestinal recovery compared to low-dose (0.5 μg/kg + 0.2 μg/kg/hour). Low-dose regimen demonstrated superior safety: High-dose dexmedetomidine significantly increased intraoperative bradycardia risk (19.15% vs 8.19% in controls, P < 0.05). Reduced opioid/sedative requirements: Dexmedetomidine groups required less propofol and remifentanil than controls, potentially mitigating opioid-induced gastrointestinal dysfunction. Clinical recommendation: Low-dose dexmedetomidine is optimal for enhancing gastrointestinal recovery while minimizing cardiovascular risks.

INTRODUCTION

Postoperative gastrointestinal recovery (POGIR) is a crucial factor affecting the rehabilitation of surgical patients. The recovery of gastrointestinal function is often a determinant of the overall recovery process, influencing the length of hospital stay and the patient’s quality of life[1]. Postoperative gastrointestinal dysfunction (POGD) is characterized by symptoms such as ileus, nausea, vomiting, and abdominal distension. POGD may prolong hospital stay and increase medical costs. In severe cases, POGD can even lead to reoperations, unplanned readmission, and increased mortality[2,3]. Therefore, promoting the recovery of postoperative gastrointestinal function has always been a hot topic in clinical research.

Dexmedetomidine, a highly selective α2-adrenergic receptor agonist, exerts effects including sedation, analgesia, anxiolysis, and sympathetic inhibition[4]. In recent years, studies have found that perioperative use of dexmedetomidine can promote the recovery of postoperative gastrointestinal function[5,6]. Intravenous administration of a loading dose of 0.5 μg/kg dexmedetomidine followed by a continuous infusion of 0.2 μg/kg/hour enhanced postoperative gastrointestinal motility function[7,8]. Studies have shown that an additional 1 μg/kg loading dose of dexmedetomidine is an independent protective factor for POGIR but may result in a lower heart rate[9]. However, in a study of 12 healthy volunteers, a loading dose of 1 μg/kg dexmedetomidine followed by a continuous infusion of 0.7 μg/kg markedly inhibited gastric emptying and gastrointestinal transit[10]. It seems different doses of dexmedetomidine may have different effects on postoperative gastrointestinal function.

However, existing literature primarily examines single-dose dexmedetomidine regimens. In these studies, dosing typically involves an initial intravenous bolus of 0.5 to 1 μg/kg administered over 10-15 minutes, followed by a continuous intravenous infusion maintained at 0.2 to 0.7 μg/kg/hour[7-9,11]. No studies have directly compared the efficacy of different doses of dexmedetomidine for laparoscopic colorectal surgery. In our hospital, the dosage selection of dexmedetomidine is generally based on the preferences of anesthesiologists. Some anesthesiologists follow the dosage recommended in the drug label, which the initial dosage is 1 μg/kg for intravenous infusion for 10 to 15 minutes, and then maintained at 0.2 to 0.7 μg/kg/hour by intravenous infusion, while others, based on clinical experience, reduce the dexmedetomidine dosage to mitigate cardiovascular adverse effects[7,8]. As addition of dexmedetomidine to promote post-operational gastrointestinal function recovery is not a standard practice, some anesthesiologists do not use it. Therefore, zero-dose, low-dose (load: 0.5 μg/kg; maintenance: 0.2 μg/kg/hour), and high-dose (load: 1.0 μg/kg; maintenance: 0.5 μg/kg/hour) regimens are administered within our hospital. Therefore, this retrospective study evaluated zero-dose, low-dose, and high-dose dexmedetomidine regimens to identify the optimal dosage for enhancing POGIR and reducing cardiovascular adverse reactions in patients undergoing laparoscopic colorectal surgery.

MATERIALS AND METHODS

Study design and population

This retrospective study included adult patients who underwent laparoscopic colorectal surgery at Longyan First Hospital between January 2023 and December 2024. The study was approved by the Institutional Ethics Committee of our hospital (No. LYREC2025-k083-01). All participants were adults aged over 18 years, classified as American Society of Anesthesiologists (ASA) physical status I-III, and underwent elective laparoscopic colorectal procedures with surgical durations ranging from 1 to 6 hours. We excluded patients who had prior abdominal surgery, unplanned reoperations, or preexisting conditions such as gastrointestinal motility disorders, severe hepatic/renal impairment, cardiac conduction abnormalities (e.g., sick sinus syndrome, atrioventricular block, sinus bradycardia), allergies to dexmedetomidine or anesthetic agents, or psychiatric disorders (Figure 1).

Figure 1  The research flow chart of 879 patients who underwent laparoscopic colorectal surgery recruited from January 2023 to December 2024.

Treatment protocols

Anesthesia was induced with intravenous sufentanil (0.2 to 0.3 μg/kg), propofol (1.0 to 2.5 mg/kg), and cisatracurium (0.2 mg/kg). Maintenance anesthesia was achieved through continuous intravenous infusion of propofol (50 to 100 μg/kg/minute), remifentanil (0.1 to 1.0 μg/kg/minute), and cisatracurium (1 to 2 μg/kg/minute), maintaining a Bispectral index value between 45-60. Standard intraoperative monitoring included electrocardiography, non-invasive blood pressure measurement, and pulse oximetry.

Patients were divided into three groups based on dexmedetomidine (Sichuan Meidakang Huakang Pharmaceutial Co., Ltd) administration: (1) Control group: No dexmedetomidine was administered; (2) Low-dose group: Received a dexmedetomidine loading dose of 0.5 μg/kg (infused over 10 minutes) prior to anesthesia induction, followed by continuous intravenous infusion at 0.2 μg/kg/hour until 30 minutes before surgical conclusion; and (3) High-dose group: Received a dexmedetomidine loading dose of 1.0 μg/kg (infused over 10 minutes) prior to anesthesia induction, followed by continuous intravenous infusion at 0.5 μg/kg/hour until 30 minutes before surgical conclusion.

All patients received 5 mg tropisetron intravenously for postoperative nausea and vomiting prophylaxis. Postoperative analgesia was maintained using a patient-controlled intravenous analgesia (PCIA) pump containing 100 μg sufentanil and 200 mg flurbiprofen axetil diluted in 150 mL normal saline. The PCIA protocol included a 3 mL loading dose, 3 mL/hour background infusion, and 2 mL patient-controlled bolus doses with a 30-minute lockout interval.

Outcome measures

Surgical and anesthetic data were retrieved, including site of surgery, duration of surgery and anesthesia, time to tracheal extubation, and intraoperative doses of dexmedetomidine, sufentanil, remifentanil, and propofol.

The primary outcome measure was the time to first flatus. Secondary outcomes included time to first defecation, time to first oral intake, and the postoperative 7-day intake, feeling nauseated, emesis, physical examination, and duration of symptoms (I-FEED) score. The I-FEED score evaluates five domains (tolerance of oral intake, nausea, vomiting, abdominal distension, and symptom duration), each score 0-2. Patients were categorized into three groups: Normal (score: 0-2), postoperative gastrointestinal intolerance (POGI) (score: 3-5), and postoperative ileus (score: ≥ 6).

Safety

Intraoperative adverse events were retrieved, including bradycardia (heart rate < 43 bpm), tachycardia (heart rate > 120 bpm), hypertension (mean arterial pressure > 20% above baseline or systolic blood pressure > 160 mmHg), and hypotension (mean arterial pressure < 20% below baseline or systolic blood pressure < 80 mmHg). Serious cardiovascular or cerebrovascular events occurring within 30 days postoperatively were also recorded.

Statistical analysis

Data were analyzed using SPSS 20.0. Continuous variables with normal distribution are presented as mean ± SD and compared using independent t-tests (two groups) or one-way analysis of variance (three groups). The least significant difference test was used for multiple comparison adjusted in one way analysis of variance. Categorical variables are presented as frequency (%) and analyzed with χ² tests. Multiple linear regression was used to analyze factors related to the time to first flatus. A P value < 0.05 was considered statistically significant.

RESULTS

Baseline characteristics

Following screening, a total of 879 patients undergoing laparoscopic colorectal cancer surgery were enrolled, including 281 in the control group, 313 in the low-dose group, and 285 in the high-dose group. No statistically significant differences were observed in baseline demographic or clinical characteristics among the three groups (P > 0.05, Table 1).

Table 1 Comparison of baseline characteristics among the three groups, mean ± SD/n (%).

Item	Control (n = 281)	Low-dose (n = 313)	High-dose (n = 285)
Age (year)	66.94 ± 8.68	65.91 ± 8.76	66.32 ± 9.14
Gender
Male	159 (56.58)	175 (55.91)	170 (59.65)
Female	122 (43.41)	138 (44.08)	115 (40.35)
BMI (kg/m2)	23.65 ± 3.03	23.78 ± 3.73	24.82 ± 3.44
ASA grading
I	8 (2.84)	14 (4.47)	11 (3.86)
II	228 (81.14)	265 (84.66)	243 (85.26)
III	45 (16.01)	34 (10.86)	31 (10.88)
Hypertension	41 (14.59)	32 (10.22)	35 (12.28)
Diabetes	14 (4.98)	10 (3.19)	17 (5.96)
Coronary heart disease	23 (8.19)	26 (8.31)	20 (7.02)

BMI: Body mass index; ASA: American Society of Anesthesiologists.

No statistically significant differences were observed among the three patient groups regarding surgical site, operative duration, or anesthesia time (P > 0.05 for all). Patients in the high-dose group demonstrated a significantly longer time to tracheal extubation during recovery compared to the control group (P < 0.05). Both low- and high-dose groups required lower propofol and remifentanil doses compared to the control group, while the high-dose group additionally showed reduced sufentanil requirements relative to controls (P < 0.05 for all, Table 2).

Table 2 Comparison of indicators related to surgical and anesthesia among the three groups, mean ± SD/n (%).

Item	Control (n = 281)	Low-dose (n = 313)	High-dose (n = 285)
Site of surgery
Proctectomy	88 (31.32)	96 (30.67)	102 (35.79)
Colectomy	193 (68.68)	217 (69.33)	183 (64.21)
Right hemicolectomy	122 (43.41)	141 (45.05)	113 (39.65)
Left hemicolectomy	61 (21.71)	63 (20.13)	59 (20.70)
Total colectomy	10 (3.56)	13 (4.15)	11 (3.86)
Operation time (minute)	207.97 ± 22.35	210.42 ± 23.03	208.97 ± 22.79
Anesthesia time (minute)	283.80 ± 23.17	285.25 ± 24.06	286.60 ± 25.06
Extubate time (minute)	21.54 ± 4.95	22.29 ± 6.47	23.20 ± 6.65a,1
Dose of dexmedetomidine (μg)	0	69.97 ± 11.71	159.51 ± 27.71a,2
Propofol (mg)	1080.72 ± 197.13	1002.78 ± 184.6a,1	1005.08 ± 183.30a,1
Sufentanil (μg)	27.52 ± 5.41	26.74 ± 5.53	26.18 ± 5.12a,1
Remifentanil (mg)	3.28 ± 0.63	2.67 ± 0.51a,1	2.59 ± 0.50a,1
Cisatracurium (mg)	23.10 ± 2.52	22.89 ± 2.62	23.24 ± 2.73

^aP < 0.05.

¹P compared with the control group.

²P compared with low-dose group.

Primary outcome

The time to first flatus in both the low-dose and high-dose groups was significantly shorter than that in the control group (65.56 ± 5.15 hours and 64.80 ± 4.90 hours vs 76.21 ± 5.32 hours, respectively; P < 0.05 for both). However, no statistically significant difference was observed between the low-dose and high-dose groups (P > 0.05).

Secondary outcomes

The time to first defecation and time to first oral intake in both the low-dose and high-dose groups were significantly shorter compared to the control group (P < 0.05 for both). Furthermore, the I-FEED score indicated a lower incidence of POGI in the low-dose and high-dose groups than in the control group (P < 0.05) (Table 3).

Table 3 Comparison of postoperative gastrointestinal function among the three groups, mean ± SD/n (%).

	Control (n = 281)	Low-dose (n = 313)	High-dose (n = 285)	Low-dose vs control MD (95%CI)	High-dose vs control MD (95%CI)
Time to first flatus (hour)	76.21 ± 5.32	65.56 ± 5.15a	64.80 ± 4.90a	-10.658 (-11.484 to -9.831)	-11.410 (-12.255 to -15.565)
Time to first faces (hour)	96.03 ± 5.14	83.68 ± 5.37a	82.91 ± 5.47a	-12.356 (-13.215 to -11.496)	-13.134 (-14.013 to -12.255)
Time to first oral feeding (hour)	85.02 ± 5.40	73.65 ± 4.95a	72.88 ± 4.80a	-11.372 (-12.187 to -10.558)	-12.141 (-12.974 to -11.308)
I-FEED score
Normal	197 (70.11)	250 (79.97)a	221 (77.54)a
POGI	65 (23.13)	45 (14.48)a	43 (15.09)a
POI	19 (6.76)	18 (5.75)	21 (7.37)

^aP < 0.05.

P compared with the control group. MD: Mean difference; CI: Confidence interval; I-FEED score: Intake, feeling nauseated, emesis, physical examination, and duration of symptoms; POGI: Postoperative gastrointestinal intolerance; POI: Postoperative ileus.

Multivariate regression analysis

Using multivariate regression analysis, the regression equation was significant (P < 0.001). Among them, dexmedetomidine group were significantly correlated with the time to first flatus (β = -10.658, P < 0.001). However, age, gender, body mass index (BMI), ASA classification, comorbidities and surgical site not correlated with the time to first flatus (all P > 0.05). These variables explained 50.20% of the variance in time to first flatus (Table 4).

Table 4 Multiple linear regression analysis results of various factors on the time to first flatus after laparoscopic colorectal surgery in patients.

Item	Simple linear regression			Multiple linear regression
	β value	t value	P value	β value	t value	P value
Constant	78.428	41.315	< 0.001	76.214	249.397	< 0.001
Age	-0.019	-0.925	0.355
Gender	0.009	0.026	0.979
BMI	-0.039	-0.76	0.447
ASA grading
II	0.126	0.138	0.890
III	-0.582	-0.52	0.603
Comorbidities	0.277	0.544	0.586
Site of surgery	-0.207	-0.559	0.577
Groups
Dexmedetomidine	-10.707	-25.234	< 0.001	-10.658	-25.316	< 0.001
High-dose dexmedetomidine	-0.746	-1.769	0.077	-0.752	-1.794	0.073

BMI: Body mass index; ASA: American Society of Anesthesiologists; Comorbidities: Hypertension, diabetes and coronary heart disease; Site of surgery: Proctectomy and colectomy.

Subgroup analysis

Subgroup analysis by gender revealed that female patients undergoing laparoscopic colorectal surgery who received high-dose dexmedetomidine experienced a significantly shorter time to first postoperative flatus (P < 0.05) (Table 5).

Table 5 Comparison of the time to first flatus was analyzed by gender subgroups, mean ± SD.

Time to first flatus (hour)	Control	Low-dose	High-dose	High-dose vs low-dose MD (95%CI)
Male	76.22 ± 5.36	65.82 ± 5.01a,1	65.65 ± 5.06a,1	-0.168 (-1.251 to 0.923)
Female	76.20 ± 5.27	65.22 ± 5.31a,1	63.55 ± 4.38a,1,2	-1.1677 (-3.114 to 0.239)

^aP < 0.05.

¹P compared with the control group.

²P compared with low-dose group.

MD: Mean difference; CI: Confidence interval.

Safety

No statistically significant differences were observed in the intraoperative incidence of tachycardia, hypotension, or hypertension among the three groups (P > 0.05). However, the high-dose group exhibited a significantly higher incidence of bradycardia compared to the control group (19.15% vs 8.19%, P < 0.05). No major cardiovascular or cerebrovascular events occurred within 30 days postoperatively in any group (Table 6).

Table 6 Comparison of the incidence of perioperative adverse events among the three groups, n (%).

	Control (n = 281)	Low-dose (n = 313)	High-dose (n = 285)
Bradycardia	23 (8.19)	41 (13.10)	56 (19.65)a
Tachycardia	16 (5.69)	15 (4.79)	13 (4.56)
Hypotension	31 (11.03)	39 (12.46)	40 (14.18)
Hypertension	35 (12.46)	31 (9.90)	25 (8.77)

^aP < 0.05.

P compared with the control group.

DISCUSSION

This retrospective study analyzed the effects of different dexmedetomidine dosages on POGIR in patients undergoing laparoscopic colorectal surgery. The results show that both low-dose and high-dose dexmedetomidine regimens significantly accelerated POGIR compared to the control group, as evidenced by reduced time to first flatus, defecation, and oral intake. The results align with prior studies demonstrating dexmedetomidine’s positive impact on postoperative gastrointestinal function[5,6]. Our study provides new insights into this area and supports the use of low-dose regimens.

Multivariate regression analysis showed that age, gender, BMI, ASA classification, comorbidities and surgical site were not significantly correlated with the time to first flatus. I-FEED score effectively evaluates postoperative gastrointestinal function recovery in patients undergoing laparoscopic colorectal surgery[12]. The results showed a lower incidence of POGI and a higher incidence of normal postoperative gastrointestinal function in both the low-dose and high-dose dexmedetomidine regimens compared with the control group. Subgroup analysis showed no significant difference in the time to first postoperative flatus between male patients receiving low-dose or high-dose dexmedetomidine. Although high-dose dexmedetomidine provided an additional reduction in the time to first postoperative flatus for female patients undergoing laparoscopic colorectal surgery compared to low-dose, the reduction was only 1 hour, a difference of limited clinical significance, while significantly compromising safety. Therefore, we recommend low-dose dexmedetomidine as the preferred regimen for both male and female patients.

As a selective α2-adrenoceptor agonist, dexmedetomidine enhances gastrointestinal motility by inhibiting catecholamine-mediated enteric neuronal activity and promoting smooth muscle contraction[13]. Preclinical studies indicate that α2-adrenoceptor activation improves intestinal blood flow and mitigates inflammatory responses, both critical for POGIR[14]. Notably, reduced intraoperative opioid (remifentanil) and sedative (propofol) requirements in the dexmedetomidine groups may indirectly benefit gastrointestinal function, as opioids are known to suppress peristalsis[15,16].

However, the high-dose regimen conferred no additional clinical benefits and was associated with a higher incidence of intraoperative bradycardia. These findings suggest that while dexmedetomidine facilitates POGIR, its effect is not dose dependent, supporting the preferential use of low-dose regimens in clinical practice. The absence of a dose-dependent relationship in dexmedetomidine’s gastrointestinal benefits suggests a potential “ceiling effect”, wherein higher doses fail to amplify therapeutic outcomes. This may reflect maximal sympathetic inhibition at lower doses, with additional α2-receptor stimulation beyond this threshold yielding no further improvement in gastrointestinal motility[17,18].

The significantly elevated bradycardia risk in the high-dose group underscores the importance of dose optimization. Bradycardia and hypotension represent the most common adverse effects associated with dexmedetomidine[19]. Dexmedetomidine induces bradycardia primarily through α2-mediated vagomimetic effects, which suppress sinoatrial node activity. This effect can be clinically significant, particularly in patients with preexisting conduction abnormalities[20]. Intravenous anticholinergic agents (e.g., atropine) can counteract this vagally mediated bradycardia. Several case reports describe dexmedetomidine-associated cardiac arrest during general or regional anesthesia, as well as cardiac conduction disorders including left anterior fascicular block and first-degree atrioventricular block[21,22]. Co-administration of amiodarone with dexmedetomidine has also been implicated as a potential contributing factor in cardiac arrest events[23]. Although no severe cardiovascular complications occurred in this study, the inherent risk of bradycardia necessitates caution when administering high-dose dexmedetomidine.

Strengths of this study include its large sample size (n = 879) and standardized postoperative analgesia protocols (PCIA pumps) across groups minimized confounding from different analgesic agents. Also, we only included patients who underwent laparoscopic colorectal surgery and minimized confounding from different operations.

The study has several limitations. As a retrospective study, there may be potential selection bias. Despite comparable baseline characteristics, some confounders (e.g., intraoperative fluid management, preoperative bowel preparation) could not be excluded. Additionally, the single-center design limits generalizability, and the absence of long-term follow-up precludes assessment of complications beyond 30 days.

CONCLUSION

Both low- and high-dose dexmedetomidine regimens enhance POGIR in laparoscopic colorectal surgery patients. The low-dose regimen demonstrates superior safety, supporting its integration into multimodal enhanced recovery pathways. Prospective studies are warranted to validate these finding.

ACKNOWLEDGEMENTS

We are grateful to the patients and their families for supporting the study.