Oxycodone-dexmedetomidine vs fentanyl analgesia in septic patients after gastric perforation surgery

Abstract

BACKGROUND

Gastric perforation is a life-threatening surgical emergency that frequently leads to sepsis with significant postoperative mortality. Appropriate analgesia management is critical as it influences inflammatory response and clinical outcomes. While fentanyl is widely used, it has limitations including immunosuppression and respiratory depression. The oxycodone-dexmedetomidine combination offers potential advantages with anti-inflammatory and organ-protective properties, but comparative studies in septic patients after gastric perforation surgery are lacking.

AIM

To compare the clinical efficacy and safety of oxycodone combined with dexmedetomidine vs conventional fentanyl analgesia on clinical outcomes in patients with sepsis following gastric perforation surgery.

METHODS

Clinical data from 98 patients with sepsis following gastric perforation surgery at our hospital between March 2019 and October 2024 were retrospectively analyzed. Patients were divided into two groups based on postoperative analgesic protocols: Control group (n = 49, receiving conventional fentanyl analgesia) and intervention group (n = 49, receiving oxycodone combined with dexmedetomidine). Inflammatory markers [procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6)], hemodynamic parameters, sedation and pain scores, organ function indicators, intensive care unit (ICU) stay duration, mechanical ventilation duration, and adverse event rates were compared between the two groups.

RESULTS

Baseline characteristics were comparable between the two groups (P > 0.05). Compared with the control group, the intervention group demonstrated significantly lower levels of PCT, CRP, and IL-6 on postoperative days 3 and 5 (all P < 0.05). Hemodynamic stability was superior in the intervention group, with smaller fluctuations in heart rate and mean arterial pressure (all P < 0.05). Richmond Agitation-Sedation Scale scores indicated better sedation quality in the intervention group, with lower Critical Care Pain Observation Tool scores at all time points (all P < 0.05). The intervention group showed significantly shorter ICU stay duration and mechanical ventilation duration (all P < 0.01). The incidence of delirium was significantly lower in the intervention group compared with the control group (8.2% vs 24.5%, P = 0.031). No significant difference was observed in the incidence of respiratory depression between the two groups (P > 0.05).

CONCLUSION

Oxycodone combined with dexmedetomidine provides superior analgesia and sedation effects compared with conventional fentanyl in patients with sepsis following gastric perforation surgery, effectively reducing inflammatory response, maintaining hemodynamic stability, shortening ICU stay duration, and decreasing the incidence of delirium, demonstrating favorable clinical application value.

Key Words: Oxycodone; Dexmedetomidine; Fentanyl; Sepsis; Gastric perforation; Analgesia; Sedation

Core Tip: Sepsis following gastric perforation surgery is associated with high morbidity and prolonged intensive care unit (ICU) stay. Optimizing postoperative analgesia and sedation may influence inflammatory response and organ recovery in these patients. This retrospective cohort study demonstrates that oxycodone combined with dexmedetomidine provides superior analgesia and sedation compared with conventional fentanyl, with improved inflammatory control, enhanced hemodynamic stability, shorter ICU stay, reduced mechanical ventilation duration, and a lower incidence of delirium. These findings support the clinical value of dexmedetomidine-based multimodal analgesia strategies in septic patients after gastric perforation surgery.

INTRODUCTION

Gastric perforation represents a severe surgical emergency characterized by sudden onset and rapid disease progression, often leading to diffuse peritonitis and sepsis[1]. With the development of surgical techniques and perioperative management, the survival rate of gastric perforation patients has significantly improved, but sepsis-related complications remain major causes of postoperative mortality[2]. Sepsis is defined as life-threatening organ dysfunction caused by dysregulated host response to infection, accompanied by complex pathophysiological changes including systemic inflammatory response, immune dysfunction, and microcirculatory disturbance[3]. For patients with sepsis following gastric perforation surgery, appropriate analgesia and sedation management not only alleviates patient discomfort but also plays a crucial role in controlling inflammatory response and improving clinical outcomes.

Fentanyl, as a commonly used opioid analgesic in intensive care unit (ICU), has been widely applied in postoperative analgesia for critically ill patients due to its rapid onset and potent analgesic effects[4]. However, traditional fentanyl analgesia has certain limitations, including immunosuppressive effects, risk of respiratory depression, and potential for accumulation with prolonged use, which may adversely affect the recovery of septic patients[5]. In recent years, multimodal analgesia strategies have gained increasing attention in ICU sedation and analgesia management, among which the combination of oxycodone and dexmedetomidine has shown unique advantages.

Oxycodone, a semi-synthetic opioid with dual agonist activity at μ and κ opioid receptors, provides effective analgesia for both somatic and visceral pain[6]. Compared with fentanyl, oxycodone demonstrates more stable hemodynamic effects and lower incidence of respiratory depression. Dexmedetomidine, a highly selective α2-adrenergic receptor agonist, not only provides sedation and anxiolysis but also exhibits anti-inflammatory and organ-protective effects[7]. Studies have shown that dexmedetomidine can reduce the release of inflammatory mediators, improve microcirculation, and decrease the incidence of delirium in critically ill patients[8].

Currently, research on the application of oxycodone combined with dexmedetomidine in septic patients following gastrointestinal surgery remains relatively limited. Specifically, there is a lack of direct head-to-head comparisons between oxycodone-dexmedetomidine combination therapy and conventional fentanyl analgesia in the specific population of patients with sepsis following gastric perforation surgery. While individual studies have examined these agents separately or in other surgical contexts, the comparative clinical efficacy, safety profile, and impact on inflammatory response and organ function in this high-risk population require further investigation[9]. Based on this background, the present study aims to compare the clinical outcomes of oxycodone combined with dexmedetomidine vs conventional fentanyl analgesia in patients with sepsis following gastric perforation surgery, providing scientific evidence for optimizing analgesia and sedation strategies in this patient population.

MATERIALS AND METHODS

Study design

This study retrospectively analyzed patients with sepsis following gastric perforation surgery admitted to our hospital between March 2019 and October 2024, evaluating the impact of different analgesic protocols on clinical outcomes.

Study population

Inclusion criteria: (1) Age between 18 years and 75 years; (2) Diagnosis of gastric perforation confirmed by imaging or surgery; (3) Meeting sepsis-3 diagnostic criteria with Sequential Organ Failure Assessment (SOFA) score ≥ 2; (4) Underwent emergency repair surgery for gastric perforation; (5) Admitted to ICU for postoperative monitoring and treatment; and (6) Complete clinical data with comprehensive follow-up records.

Exclusion criteria: (1) History of allergy to study drugs (oxycodone, dexmedetomidine, fentanyl); (2) Severe cardiac dysfunction (NYHA class IV); (3) Severe hepatic or renal insufficiency; (4) History of drug abuse or chronic opioid use; (5) Requirement for reoperation within 24 hours postoperatively; (6) Cognitive impairment or psychiatric disorders preventing cooperation with assessment; and (7) Pregnant or lactating women.

Surgical procedures

All surgical procedures were performed by attending physicians or associate chief physicians with more than 10 years of gastrointestinal surgical experience. Surgical approach included primary repair, omental patch repair, or partial gastrectomy based on the size and location of perforation and degree of peritoneal contamination. Thorough abdominal lavage was performed with warm saline, and drainage tubes were routinely placed. All patients received standard anti-tuberculosis or anti-infective treatment postoperatively. Surgical approach selection was primarily based on comprehensive assessment of perforation characteristics, duration of symptoms, and patient general condition.

Group assignment

Patients were divided into two groups according to different postoperative analgesic protocols: (1) Control group (n = 49): Received conventional fentanyl analgesia; and (2) Intervention group (n = 49): Received oxycodone combined with dexmedetomidine. Patient assignment to treatment groups was based on the analgesic protocol implemented during the study period. From March 2019 to June 2021, conventional fentanyl-based analgesia was the standard protocol in our ICU, and patients admitted during this period constituted the control group. From July 2021 to October 2024, following institutional protocol revision and based on emerging evidence supporting multimodal analgesia, our ICU adopted oxycodone combined with dexmedetomidine as the standard analgesic protocol for septic patients following gastric perforation surgery, and patients admitted during this period constituted the intervention group. This sequential assignment was determined by institutional protocol changes rather than individual physician discretion or patient-specific characteristics. We acknowledge that this non-randomized, time-based assignment introduces potential for confounding by temporal trends and indication bias, which we address through rigorous baseline comparison and statistical adjustment, and discuss as a major limitation of this study.

Ethics statement

This retrospective study was conducted in accordance with the Declaration of Helsinki and was approved by the Ethics Committee of Hejian Branch of Cangzhou Central Hospital, ethics approval No. 2025-1091-01(z). Due to the retrospective nature of this study utilizing de-identified data from medical records, and considering that both analgesic protocols evaluated represent standard clinical care implemented according to institutional protocols rather than experimental interventions, the Ethics Committee granted a waiver of informed consent requirement.

Intervention measures

Control group (conventional fentanyl analgesia): Patients in the control group received conventional fentanyl-based analgesia protocol: Initial intravenous bolus of fentanyl 50-100 μg, followed by continuous infusion at 25-100 μg/hour, adjusted according to pain assessment scores. Propofol was added for sedation when necessary, with infusion rate adjusted to maintain Richmond Agitation-Sedation Scale (RASS) score between -2 and 0. Pain assessment was performed every 4 hours using the Critical Care Pain Observation Tool (CPOT), with target score ≤ 2.

Intervention group (oxycodone combined with dexmedetomidine): Patients in the intervention group received a combined analgesic protocol, with specific measures as follows: (1) Oxycodone administration: Initial intravenous bolus of oxycodone 2-5 mg, followed by continuous infusion at 0.5-2 mg/hour, adjusted according to pain assessment scores. Pain assessment performed every 4 hours using CPOT, with target score ≤ 2; (2) Dexmedetomidine administration: Loading dose of 0.5-1.0 μg/kg infused over 10-20 minutes (may be omitted in hemodynamically unstable patients), followed by continuous infusion at 0.2-0.7 μg/(kg/hour). Infusion rate adjusted to maintain RASS score between -2 and 0; (3) Dose adjustment principles: For patients with hypotension [mean arterial pressure (MAP) < 65 mmHg], dexmedetomidine dose was reduced or temporarily suspended; for patients with bradycardia (heart rate < 50 beats/min), dexmedetomidine was dose reduced or atropine administered as needed; (4) Target-directed sedation: Daily sedation interruption performed when patient condition permitted, assessing neurological status and adjusting medication dosages; (5) Monitoring protocol: Continuous monitoring of heart rate, blood pressure, respiratory rate, and oxygen saturation. Arterial blood gas analysis performed every 6-8 hours. Delirium assessment using Confusion Assessment Method for ICU (CAM-ICU) performed twice daily; and (6) Weaning protocol: When sepsis indicators improved and patient condition stabilized, gradual dose reduction of both oxycodone and dexmedetomidine was initiated, with complete discontinuation typically achieved within 24-48 hours.

Observation indicators

General data: Basic demographic characteristics and clinical data of both groups were recorded, including: Age, gender, body mass index (BMI), comorbidities (hypertension, diabetes, coronary heart disease), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, SOFA score on admission, perforation size, time from symptom onset to surgery, and surgical approach.

Inflammatory markers: (1) Procalcitonin (PCT): Measured on admission, postoperative days 1, 3, and 5 (ng/mL); (2) C-reactive protein (CRP): Measured on admission, postoperative days 1, 3, and 5 (mg/L); (3) Interleukin-6 (IL-6): Measured on admission, postoperative days 1, 3, and 5 (pg/mL); and (4) White blood cell count: Measured on admission, postoperative days 1, 3, and 5 (× 10⁹/L).

Hemodynamic parameters: (1) MAP: Recorded at 6 hours, 12 hours, 24 hours, and 48 hours postoperatively (mmHg); (2) Heart rate: Recorded at 6 hours, 12 hours, 24 hours, and 48 hours postoperatively (beats/min); (3) Vasopressor requirements: Norepinephrine dose and duration of use; and (4) Cardiac index: Measured at 24 hours and 48 hours postoperatively (L/min/m²).

Sedation and pain assessment: (1) RASS score: Assessed every 4 hours, target range -2 to 0; (2) Critical CPOT score: Assessed every 4 hours, target ≤ 2; (3) Time to achieve target sedation level (hours); (4) Total opioid consumption (morphine equivalent dose, mg); and (5) Incidence of over-sedation (RASS < -3).

Organ function indicators: (1) Renal function: Serum creatinine, blood urea nitrogen, urine output; (2) Hepatic function: Alanine aminotransferase, aspartate aminotransferase, total bilirubin; (3) Respiratory function: PaO₂/FiO₂ ratio, mechanical ventilation duration (hours); and (4) Lactate levels: Measured on admission, postoperative days 1, 2, and 3 (mmol/L).

Clinical outcomes: (1) ICU length of stay (days); (2) Hospital length of stay (days); (3) 28-day mortality rate; (4) Incidence of delirium (assessed by CAM-ICU); (5) Incidence of respiratory depression (respiratory rate < 10 breaths/min or SpO₂ < 90%); and (6) Other adverse events: Bradycardia, hypotension, nausea and vomiting.

Statistical analysis

Data analysis was performed using SPSS version 26.0 statistical software. All continuous variables were first subjected to normality testing (Shapiro-Wilk test). Normally distributed quantitative data were presented as mean ± SD, with independent samples t-test used for between-group comparisons; non-normally distributed quantitative data were presented as median and interquartile range [M (Q1, Q3)], with Mann-Whitney U test used for between-group comparisons. Categorical variables were presented as n (%), with χ² test or Fisher’s exact test (when expected frequency < 5) used for between-group comparisons. Repeated measures data were analyzed using repeated measures ANOVA. All statistical tests were two-sided, with P < 0.05 considered statistically significant.

RESULTS

The following results represent observed associations between treatment protocols and clinical outcomes. Due to the retrospective, non-randomized design of this study, these findings should be interpreted as associations rather than definitive causal effects. The potential influence of unmeasured confounding factors and indication bias must be considered when evaluating these results.

Comparison of general data

A total of 98 patients were enrolled. No significant differences were observed in baseline characteristics including age, gender, BMI, comorbidities, APACHE II score, SOFA score, and perforation size between the two groups (P > 0.05), indicating comparability (Table 1).

Table 1 Comparison of general data between two groups, mean ± SD.

Item	Control group (n = 49)	Intervention group (n = 49)	Statistic	P value
Age (years)	56.8 ± 12.4	55.3 ± 13.1	t = 0.580	0.563
Gender, male, n (%)	31 (63.3)	29 (59.2)	χ2 = 0.173	0.677
BMI (kg/m2)	23.5 ± 3.2	24.1 ± 3.5	t = 0.879	0.382
APACHE II score	18.6 ± 4.8	17.9 ± 5.1	t = 0.698	0.487
SOFA score	7.2 ± 2.3	6.9 ± 2.1	t = 0.670	0.504
Perforation size (cm)	1.8 ± 0.7	1.9 ± 0.8	t = 0.654	0.514

BMI: Body mass index; APACHE II: Acute Physiology and Chronic Health Evaluation II; SOFA: Sequential Organ Failure Assessment.

Comparison of inflammatory markers

On postoperative days 3 and 5, patients in the intervention group demonstrated significantly lower levels of PCT, CRP, and IL-6 compared with the control group (all P < 0.05), indicating more effective control of inflammatory response (Table 2).

Table 2 Comparison of inflammatory markers between two groups, mean ± SD.

Item	Control group (n = 49)	Intervention group (n = 49)	t value	P value
PCT on admission (ng/mL)	12.8 ± 5.6	13.2 ± 6.1	0.336	0.738
PCT on POD 3 (ng/mL)	6.4 ± 3.2	4.8 ± 2.5	2.746	0.007
PCT on POD 5 (ng/mL)	3.1 ± 1.8	1.9 ± 1.2	3.858	< 0.001
CRP on POD 3 (mg/L)	124.8 ± 36.2	98.6 ± 28.5	3.964	< 0.001
CRP on POD 5 (mg/L)	68.4 ± 22.6	48.2 ± 18.3	4.832	< 0.001
IL-6 on POD 3 (pg/mL)	168.5 ± 52.3	128.6 ± 42.8	4.112	< 0.001
IL-6 on POD 5 (pg/mL)	86.2 ± 28.4	62.5 ± 21.6	4.611	< 0.001

PCT: Procalcitonin; CRP: C-reactive protein; IL-6: Interleukin-6; POD: Postoperative day.

Comparison of hemodynamic parameters

The intervention group demonstrated superior hemodynamic stability with smaller MAP fluctuations and more stable heart rate at 12 hours, 24 hours, and 48 hours postoperatively (all P < 0.05). No significant difference was observed in vasopressor requirements (P > 0.05) (Table 3).

Table 3 Comparison of hemodynamic parameters between two groups, mean ± SD.

Item	Control group (n = 49)	Intervention group (n = 49)	t value	P value
MAP at 12 hours (mmHg)	74.8 ± 9.2	78.6 ± 7.4	2.243	0.027
MAP at 24 hours (mmHg)	76.2 ± 8.4	80.8 ± 6.8	2.954	0.004
MAP at 48 hours (mmHg)	78.5 ± 7.6	82.4 ± 5.9	2.808	0.006
HR at 24 hours (bpm)	92.4 ± 12.6	86.2 ± 10.4	2.636	0.010
HR at 48 hours (bpm)	88.2 ± 10.8	82.6 ± 8.6	2.812	0.006

MAP: Mean arterial pressure; HR: Heart rate.

Comparison of sedation and pain assessment

The intervention group achieved target sedation faster with lower CPOT scores at all time points (all P < 0.05). Total opioid consumption was significantly lower in the intervention group (124.8 ± 35.2 mg vs 168.4 ± 42.6 mg, P < 0.001) (Table 4).

Table 4 Comparison of sedation and pain assessment between two groups, mean ± SD.

Item	Control group (n = 49)	Intervention group (n = 49)	Statistic	P value
Time to target sedation (hours)	3.8 ± 1.4	2.6 ± 1.1	t = 4.692	< 0.001
CPOT at 6 hours	2.4 ± 0.8	1.8 ± 0.6	t = 4.167	< 0.001
CPOT at 24 hours	1.9 ± 0.7	1.4 ± 0.5	t = 4.037	< 0.001
Total opioid (MEQ mg)	168.4 ± 42.6	124.8 ± 35.2	t = 5.486	< 0.001

CPOT: Critical Care Pain Observation Tool; MEQ: Morphine equivalent.

Comparison of organ function indicators

The intervention group demonstrated significantly better organ function preservation. PaO₂/FiO₂ ratio was significantly higher on postoperative days 3 and 5 (all P < 0.01). Serum creatinine levels were significantly lower (all P < 0.05). SOFA scores declined more rapidly in the intervention group (all P < 0.01) (Table 5 and Figure 1).

Figure 1 Dynamic changes of organ function indicators. A: PaO₂/FiO₂ ratio changes over time showing significantly faster improvement in the intervention group; B: Sequential Organ Failure Assessment score changes demonstrating more rapid decline in the intervention group. ^aP < 0.01 vs control group. POD: Postoperative day; SOFA: Sequential Organ Failure Assessment.

Table 5 Comparison of organ function indicators between two groups, mean ± SD.

Item	Control group (n = 49)	Intervention group (n = 49)	t value	P value
PaO2/FiO2 on admission (mmHg)	186.4 ± 42.8	182.6 ± 45.2	0.424	0.672
PaO2/FiO2 on POD 3 (mmHg)	218.6 ± 48.5	256.4 ± 52.8	3.676	< 0.001
PaO2/FiO2 on POD 5 (mmHg)	268.4 ± 54.2	312.6 ± 48.6	4.215	< 0.001
Creatinine on POD 3 (μmol/L)	128.6 ± 32.4	108.2 ± 28.6	3.281	0.001
Creatinine on POD 5 (μmol/L)	102.4 ± 26.8	86.5 ± 22.4	3.163	0.002
SOFA on POD 3	5.4 ± 1.8	4.2 ± 1.5	3.561	< 0.001
SOFA on POD 5	3.8 ± 1.4	2.6 ± 1.2	4.522	< 0.001

POD: Postoperative day; SOFA: Sequential Organ Failure Assessment.

Comparison of lactate metabolism

Lactate levels decreased more rapidly in the intervention group, with significantly lower values at 12 hours, 24 hours, and 48 hours (all P < 0.01). The 24-hour lactate clearance rate was significantly higher (52.8% ± 12.4% vs 38.6% ± 14.8%, P < 0.001). Time to lactate normalization was significantly shorter (32.4 ± 10.6 hours vs 46.8 ± 14.2 hours, P < 0.001) (Table 6 and Figure 2).

Figure 2 Dynamic changes of lactate metabolism. A: Arterial lactate level changes over time showing significantly faster clearance in the intervention group; B: Comparison of 24-hour lactate clearance rates between the two groups. ^aP < 0.01, ^bP < 0.001 vs control group.

Table 6 Comparison of lactate metabolism between two groups, mean ± SD.

Item	Control group (n = 49)	Intervention group (n = 49)	t value	P value
Lactate on admission (mmol/L)	4.8 ± 1.6	4.6 ± 1.5	0.634	0.528
Lactate at 12 hours (mmol/L)	3.6 ± 1.2	2.8 ± 0.9	3.712	< 0.001
Lactate at 24 hours (mmol/L)	2.9 ± 1.0	2.1 ± 0.7	4.542	< 0.001
Lactate at 48 hours (mmol/L)	2.2 ± 0.8	1.6 ± 0.5	4.412	< 0.001
24h lactate clearance rate (%)	38.6 ± 14.8	52.8 ± 12.4	5.102	< 0.001
Time to lactate normalization (hours)	46.8 ± 14.2	32.4 ± 10.6	5.632	< 0.001

Lactate clearance rate = [(initial lactate - current lactate)/initial lactate] × 100%.

Comparison of clinical outcomes

The intervention group demonstrated significantly shorter ICU stay (5.2 ± 1.9 days vs 6.8 ± 2.4 days, P < 0.001) and mechanical ventilation duration (36.2 ± 14.6 hours vs 48.6 ± 18.4 hours, P < 0.001). Delirium incidence was significantly lower (8.2% vs 24.5%, P = 0.031). No significant differences in 28-day mortality or respiratory depression were observed (Table 7).

Table 7 Comparison of clinical outcomes between two groups, n (%)/mean ± SD.

Item	Control group (n = 49)	Intervention group (n = 49)	Statistic	P value
ICU LOS (days)	6.8 ± 2.4	5.2 ± 1.9	t = 3.643	< 0.001
MV duration (hours)	48.6 ± 18.4	36.2 ± 14.6	t = 3.668	< 0.001
28-day mortality	4 (8.2)	3 (6.1)	χ2 = 0.154	0.695
Delirium incidence	12 (24.5)	4 (8.2)	χ2 = 4.653	0.031
Respiratory depression	3 (6.1)	2 (4.1)	χ2 = 0.211	0.646
Bradycardia	2 (4.1)	6 (12.2)	χ2 = 1.965	0.161

ICU: Intensive care unit; LOS: Length of stay; MV: Mechanical ventilation.

Survival analysis and subgroup outcomes

Kaplan-Meier survival analysis was performed to compare mortality outcomes between groups. The 30-day mortality rate was 12.2% (6/49) in the control group vs 6.1% (3/49) in the intervention group (log-rank P = 0.285). The 90-day mortality rate was 18.4% (9/49) in the control group vs 10.2% (5/49) in the intervention group (log-rank P = 0.246). Although the intervention group demonstrated a trend toward lower mortality at both time points, the differences did not reach statistical significance, likely due to the limited sample size and relatively low event rate.

Subgroup analyses were conducted stratified by disease severity and patient characteristics: (1) APACHE II score (< 20 vs ≥ 20); (2) SOFA score (< 8 vs ≥ 8); (3) Age (< 65 vs ≥ 65 years); and (4) Presence of shock at admission. The survival benefit of the oxycodone-dexmedetomidine protocol appeared more pronounced in patients with higher disease severity (APACHE II ≥ 20 and SOFA ≥ 8), though formal interaction testing did not reach statistical significance. In the high APACHE II score subgroup (≥ 20), 30-day mortality was 20.0% in the control group vs 8.3% in the intervention group (P = 0.18). Similarly, in the high SOFA score subgroup (≥ 8), 30-day mortality was 18.2% in the control group vs 7.7% in the intervention group (P = 0.21). Age and shock status showed less pronounced subgroup differences.

DISCUSSION

Through retrospective analysis of clinical data from 98 patients with sepsis following gastric perforation surgery, this study systematically evaluated the clinical effectiveness of oxycodone combined with dexmedetomidine vs conventional fentanyl analgesia. The results demonstrate that compared with conventional fentanyl analgesia, the combined protocol of oxycodone and dexmedetomidine exhibited significant advantages in reducing inflammatory response, maintaining hemodynamic stability, improving sedation and analgesia quality, and shortening ICU stay duration, confirming the clinical application value of this combined analgesia strategy in septic patients following gastric perforation surgery.

In this study, patients in the intervention group demonstrated significantly lower levels of inflammatory markers including PCT, CRP, and IL-6 on postoperative days 3 and 5 compared with the control group, suggesting that the combination of oxycodone and dexmedetomidine can more effectively control inflammatory response. The mechanisms underlying this anti-inflammatory effect are multifaceted. Primarily, dexmedetomidine has been shown to inhibit the release of pro-inflammatory cytokines through α2-adrenergic receptor-mediated pathways, reduce NF-κB activation, and attenuate systemic inflammatory response[10]. Additionally, adequate analgesia itself can reduce stress-induced inflammatory mediator release, forming a virtuous cycle[11]. Furthermore, the organ-protective effects of dexmedetomidine may help reduce secondary inflammation caused by tissue damage[12].

The pharmacological basis for the observed benefits involves complementary mechanisms of action. Oxycodone, as a semi-synthetic opioid with dual agonist activity at both μ and κ opioid receptors, provides effective analgesia for both somatic and visceral pain, which is particularly relevant in the context of abdominal surgery and peritonitis. The κ-receptor activity distinguishes oxycodone from pure μ-agonists like fentanyl and may contribute to superior visceral pain control with potentially less respiratory depression. Dexmedetomidine, through its highly selective α2-adrenergic receptor agonism (α2: Α1 selectivity ratio of 1620:1), produces sedation through actions in the locus coeruleus while providing analgesia through spinal and supraspinal mechanisms. Unlike GABA-ergic sedatives, dexmedetomidine produces a more natural, arousable sedation that facilitates patient cooperation and may reduce delirium risk. The combination of these agents allows for opioid dose reduction while maintaining adequate analgesia, potentially minimizing opioid-related adverse effects including immunosuppression, which is particularly concerning in septic patients whose immune function is already compromised.

Hemodynamic stability is crucial for septic patients, as both hypotension and excessive tachycardia can adversely affect organ perfusion and increase mortality risk[13]. The results of this study indicate that the intervention group demonstrated superior hemodynamic stability, with smaller fluctuations in MAP and more stable heart rate. This finding is consistent with the pharmacological characteristics of dexmedetomidine. Although dexmedetomidine may cause initial transient blood pressure elevation followed by mild hypotension, when combined with opioids, it can reduce the required opioid dosage and consequently decrease opioid-induced hemodynamic instability[14]. Oxycodone itself also demonstrates more stable hemodynamic effects compared with fentanyl, particularly in terms of histamine release and vasodilation effects[15].

Regarding sedation and analgesia quality, the intervention group demonstrated faster achievement of target sedation level and lower pain scores. This advantage is attributed to the synergistic analgesic effects of oxycodone and dexmedetomidine. Oxycodone, as a dual μ/κ receptor agonist, provides effective analgesia for both somatic and visceral pain[16]. Dexmedetomidine provides sedation through central α2 receptor activation while also exerting analgesic effects through spinal and supraspinal mechanisms, enabling significant reduction of opioid requirements[17]. This opioid-sparing effect not only reduces the risk of opioid-related adverse effects but also helps decrease drug accumulation in critically ill patients.

Notably, the incidence of delirium was significantly lower in the intervention group (8.2% vs 24.5%, P = 0.031), representing one of the important clinical benefits of this combined analgesia strategy. Delirium is a common and serious complication in ICU patients, associated with increased mortality, prolonged mechanical ventilation, and long-term cognitive impairment[18]. Dexmedetomidine has been shown in multiple studies to reduce the incidence of ICU delirium, potentially related to its unique sedation mechanism that preserves natural sleep architecture and maintains cortical activity[19]. In this study, the reduction in delirium incidence further confirms the neuroprotective advantage of dexmedetomidine in septic patients.

From the perspective of clinical outcomes, the intervention group demonstrated significantly shorter ICU length of stay and mechanical ventilation duration, which not only improves patient prognosis but also helps optimize medical resource utilization. The combined effects of reduced inflammatory response, improved sedation quality, and decreased delirium incidence may contribute to this shortened treatment course[20]. Although no significant difference was observed in 28-day mortality between the two groups, this may be related to the relatively small sample size and low overall mortality rate in this study.

Regarding safety, no significant difference was observed in the incidence of respiratory depression between the two groups, indicating that the combined protocol does not increase the risk of respiratory depression. The incidence of bradycardia was numerically higher in the intervention group, though not statistically significant, which is consistent with the known pharmacological effects of dexmedetomidine. In clinical practice, this potential adverse effect can be managed through appropriate monitoring and dose adjustment[21].

As a retrospective study, this research has certain limitations. First, the retrospective nature of the study design may introduce selection bias and information bias[22]. Second, the sample size is relatively small, and as a single-center study, the generalizability of results requires further verification. Additionally, this study was unable to evaluate long-term follow-up outcomes, such as cognitive function and quality of life at 3 months and 6 months postoperatively[23]. The degree of peritoneal contamination and severity of sepsis vary considerably among gastric perforation patients, and these factors may influence the effectiveness of different analgesic protocols, but this study was unable to conduct detailed subgroup analysis[24]. Future research should consider conducting multicenter, large-sample prospective randomized controlled trials to obtain higher-level evidence-based medical evidence.

The results of this study indicate that the application of oxycodone combined with dexmedetomidine in patients with sepsis following gastric perforation surgery is safe and effective, providing novel approaches and methods for analgesia and sedation management in this patient population. With deepening understanding of sepsis pathophysiology and continuous refinement of sedation and analgesia strategies, this combined protocol is expected to achieve broader application in critically ill surgical patients[25].

From a clinical practice perspective, successful implementation of multimodal analgesia protocols requires multidisciplinary team collaboration, including joint participation of anesthesiologists, intensivists, surgeons, and nursing personnel[26]. Simultaneously, establishment of standardized operational procedures and monitoring protocols is necessary to ensure protocol implementation standardization and safety. Medical institutions should emphasize training of relevant personnel in sedation and analgesia assessment tools and drug administration, creating favorable conditions for widespread application of optimized analgesia protocols[27].

Based on the results of this study, future research may proceed in several directions: First, conducting multicenter, large-sample prospective randomized controlled trials to further verify the application effectiveness of oxycodone combined with dexmedetomidine in septic patients[28]. Second, exploring individualized sedation and analgesia protocol development strategies, optimizing drug selection and dosing according to specific patient conditions, severity of sepsis, and organ function. Additionally, investigating synergistic effects between this combined analgesia protocol and other sepsis management strategies, such as overall effects of comprehensive measures including early goal-directed therapy, source control, and antimicrobial therapy.

This study has several important limitations that must be acknowledged. First and most importantly, the retrospective, non-randomized design represents a fundamental limitation that precludes causal inference. The observed associations between the oxycodone-dexmedetomidine protocol and improved clinical outcomes cannot be interpreted as definitive causal effects. Despite our efforts to control for measured confounders through baseline comparison and statistical adjustment, unmeasured confounding factors may have influenced the results. The time-based sequential assignment of treatment protocols introduces potential for temporal confounding, as changes in other aspects of clinical practice, institutional protocols, or patient characteristics over the study period may have contributed to the observed differences. Additionally, indication bias represents a significant concern, as the decision to implement the new protocol may have been influenced by institutional factors, staff training, or patient population characteristics that are not fully captured in our data.

CONCLUSION

In conclusion, this study confirms that oxycodone combined with dexmedetomidine provides superior clinical outcomes compared with conventional fentanyl analgesia in patients with sepsis following gastric perforation surgery, demonstrating favorable application value and providing valuable reference evidence for clinical practice. However, given the non-randomized retrospective design and the limitations inherent in such studies, these findings should be interpreted as preliminary evidence requiring validation through prospective, randomized controlled trials before definitive clinical recommendations can be made. With continuous deepening of related research and accumulation of clinical experience, this combined analgesia strategy is expected to bring benefits to more critically ill patients.