Abstract
Purpose
This study aimed to evaluate the analgesic efficacy and safety profile of varying bolus doses of hydromorphone administered via patient-controlled intravenous analgesia (PCIA) in patients undergoing laparoscopic surgery.
Patients and methods
In this randomized controlled trial, 111 patients undergoing laparoscopic surgery were randomly allocated into three groups, each receiving hydromorphone PCIA without background infusion. The groups differed by bolus dose: Group A (0.20 mg, n = 39), Group B (0.25 mg, n = 34), and Group C (0.30 mg, n = 38). All PCIA solutions consisted of hydromorphone with same concentration (10 mg diluted in 100 mL normal saline, concentration 0.1 mg/mL), with a lockout interval of 10 min. VAS scores for pain at rest and during activity at 24 h postoperatively were assessed as the primary endpoint measures. Secondary outcomes included pain intensity at rest and during activity at other time points (PACU admission, and 4, 8, 12 h postoperatively), bolus frequency, cumulative hydromorphone consumption, catheter removal time, recovery indices (time to first flatus, oral intake, ambulation), vital signs (oxygen saturation, MAP, heart rate, respiratory rate), and postoperative adverse events (postoperative nausea and vomiting [PONV], pruritus, dizzy and respiratory depression).
Results
There were no significant differences among the three groups in VAS scores at rest and during activity at 24 h postoperatively. Similarly, VAS scores at rest and during activity at PACU, 4, 8, and 12 h after surgery did not differ significantly among groups. The frequency of bolus administration was significantly higher in Group A compared to Groups B and C (P = 0.002). No significant differences were observed in total hydromorphone consumption, catheter removal time, bowel function recovery, or other recovery parameters. Although the differences were not statistically significant, the incidence of postoperative adverse events—including nausea and vomiting, pruritus, and dizziness-was lowest in Group B. No cases of respiratory depression occurred in any group.
Conclusion
Hydromorphone PCIA at bolus doses of 0.20 mg, 0.25 mg, and 0.30 mg provided equivalent analgesic effectiveness in patients following laparoscopic surgery. The 0.20 mg dose group exhibited higher bolus administration frequency, whereas the 0.25 mg dose demonstrated the lowest incidence of adverse events, suggesting an optimal balance between analgesic efficacy and side-effect profile.
Supplementary Information
The online version contains supplementary material available at 10.1186/s12871-025-03287-5.
Keywords: Hydromorphone, Patient-Controlled intravenous analgesia, Bolus dose, Laparoscopic surgery, Postoperative pain
Introduction
Postoperative pain management remains a critical component of enhanced recovery after surgery (ERAS), particularly following laparoscopic procedures, which are increasingly favored for their minimally invasive benefits yet still necessitate effective analgesia to optimize patient outcomes [1–3]. Effective postoperative pain management remains essential for enhancing patient recovery, optimizing patient satisfaction, and reducing postoperative complications following surgical procedures [4, 5]. Patient-controlled intravenous analgesia (PCIA) is well-established as an effective and patient-centered method for postoperative pain relief, allowing patients autonomy in self-administering analgesics within preset safety parameters [6–8]. Among opioids commonly employed in PCIA, hydromorphone is widely favored due to its potent analgesic effect, rapid onset, and favorable pharmacokinetic profile [9, 10].
Despite the broad clinical application of hydromorphone in PCIA regimens, the optimal bolus dose for postoperative analgesia after laparoscopic surgery remains inadequately defined [11–13]. Previous research indicates that bolus dose selection can significantly influence analgesic effectiveness, opioid consumption, patient satisfaction, and adverse event incidence [14–17]. Lower bolus doses may lead to inadequate analgesia and increased frequency of administration, whereas higher doses might elevate the risk of opioid-related adverse reactions, including nausea, vomiting, sedation, and respiratory depression.
Given these considerations, this randomized controlled trial aimed to compare the analgesic efficacy, opioid consumption, recovery parameters, and safety profiles associated with three different bolus doses of hydromorphone (0.20 mg, 0.25 mg, and 0.30 mg) in PCIA without background infusion for patients undergoing laparoscopic surgery. The results of this investigation may provide evidence-based guidance for optimizing postoperative pain management protocols.
Patients and methods
Study design
This randomized, double-blind, prospective trial was performed in compliance with the ethical principles outlined in the Declaration of Helsinki and relevant national regulations. This trial follows CONSORT guidelines. All patients received detailed information about the study, and both written and verbal informed consent were obtained. Ethical approval was granted by the Medical Ethics Committee of Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China (Approval No. 20200721-11). The study was registered with the Chinese Clinical Trial Registry (Registration No. ChiCTR2000036216; https://www.chictr.org.cn).
Participants
The study was conducted at the Department of Anesthesiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, between September 2020 and September 2021. Inclusion criteria were specified as follows: (1) patients classified as American Society of Anesthesiologists (ASA) Class I–II; (2) undergoing laparoscopic surgery; (3) cognitively intact; (4) aged between 18 and 75 years; and (5) no history of drug abuse, chronic pain conditions, psychiatric disorders, or comorbidities such as pregnancy-related complications.
Exclusion criteria included: (1) allergy to hydromorphone or its excipients; (2) recent use of opioids or non-steroidal anti-inflammatory drugs within 48 h prior to surgery; (3) dysfunction involving the heart, brain, liver, or kidneys; (4) endocrine disorders or severe infections; (5) suspected or confirmed history of alcohol or substance abuse; (6) significant psychiatric or psychological disorders, language impairments, or inability to cooperate with treatment; (7) alterations in surgical approach during the procedure; and (8) inability to comply with operational protocols.
Anesthesia protocol
All patients were instructed to abstain from solid foods for at least 8 h prior to anesthesia. Clear liquids (such as water, clear tea, and juice without pulp) were permitted up to 2 h before induction. All patients avoided preoperative usage of pain medication. Upon admission to the operating room, standard intraoperative monitoring was initiated, including electrocardiogram (ECG), systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse oximetry (SpO2). Intravenous (IV) access was established, and radial arterial cannulation was performed following a successful Allen’s test to enable invasive blood pressure monitoring.
Anesthesia induction was achieved using sufentanil (0.3 µg/kg), propofol (2 mg/kg), and Cisatracurium besilate (0.15 mg/kg). Tracheal intubation was performed 3 min after preoxygenation. Mechanical ventilation parameters were set to a tidal volume (VT) of 6–8 mL/kg, inspiratory-to-expiratory ratio (I: E) of 1:2, fraction of inspired oxygen (FiO2) of 60%, respiratory rate (RR) of 8–12 breaths/min (adjusted as needed), and end-tidal carbon dioxide (PETCO2) maintained at 35–45 mmHg. General anesthesia was maintained with remifentanil (1.5–6 µg·kg-1·h-1) and propofol (4–10 mg·kg-1·h-1) administered via syringe pump, ensuring a bispectral index (BIS) between 40 and 60. Cisatracurium was used as needed. The blood loss was estimated by collecting the blood in the negative pressure suction bottle. Vasoactive drugs were administered to stabilize blood pressure and heart rate when fluctuations exceeded 20% of baseline values. Before wound closure, 20 mL of 0.375% ropivacaine was administered for local infiltration anesthesia. For postoperative nausea and vomiting (PONV) prophylaxis, granisetron 3 mg was administered intravenously at the end of surgery.
Trial procedures
Patients meeting the inclusion criteria were randomly assigned to one of three treatment groups using a computer-generated randomization sequence. Group allocation and drug preparation were handled by a nurse not involved in outcome assessment. During the preoperative assessment, the researchers thoroughly informed patients and their families about the proper use, benefits, and potential drawbacks of the pulse-controlled analgesic pump (Rehn medtech, Jiangsu, China). Each group received a specific postoperative intravenous analgesia regimen. Hydromorphone was diluted to the same concentration (10 mg of hydromorphone diluted in 100 mL of 0.9% normal saline) with a lockout interval of 10 min and was used for all three groups. The groups differed by bolus dose: Group A (0.20 mg), Group B (0.25 mg), and Group C (0.30 mg). The screen of the analgesia pump was covered so that both patients and assessors were blinded to the bolus dose. When a patient’s VAS score exceeded 4, 50 mg of pethidine hydrochloride was administered as rescue analgesia.
Outcome measures
VAS scores for pain at rest and during activity at 24 h postoperatively were assessed as the primary endpoint measures. Activity was defined as taking three deep breaths followed by one cough [18]. Secondary outcomes included pain intensity at rest and during activity at other time points (PACU admission, and 4, 8, 12 h postoperatively), bolus frequency, cumulative hydromorphone consumption, catheter removal time, recovery indices (time to first flatus, oral intake, ambulation), vital signs (oxygen saturation, MAP, heart rate, respiratory rate). The measurement time points of vital signs are T0-T4 (Time points T0 to T4 are defined as follows: T0 at PACU admission, T1 at 4 hours postoperatively, T2 at 8 hours postoperatively, T3 at 12 hours postoperatively, and T4 at 24 hours postoperatively), and postoperative adverse events (postoperative nausea and vomiting [PONV], pruritus, dizzy and respiratory.
depression). Postoperative follow-up for pain scores was performed for 24 h, with further monitoring of recovery indices until hospital discharge.
Sample size Estimation
This study used resting pain scores as the primary outcome measure and divided participants into three groups. The required sample size was calculated using PASS 15 software (NCSS, Kaysville, Utah, USA). Based on the results of the pilot experiment, the mean pain scores after treatment were 0.83 ± 0.64, 1.22 ± 0.71, and 0.69 ± 0.58 for Groups A, B, and C, respectively. A two-sided significance level (α) of 0.05 and a statistical power (Power) of 0.80 were applied. Inputting these values into the PASS 15 software under the “One-Way Analysis of Variance F-Tests” module, the minimum required sample size per group was determined to be 34 participants. Considering a 10% dropout rate, 120 patients were initially enrolled, and 111 patients were ultimately included in the analysis.
Statistical analysis
Statistical analysis was performed using SPSS (SPSS, Inc., USA). Continuous variables were tested for normality using the Shapiro-Wilk test. Normally distributed data were expressed as mean ± SD and analyzed using one-way ANOVA with Bonferroni post-hoc corrections. Non-normally distributed data were presented as mean ± SD and compared using the Kruskal-Wallis H test, with pairwise comparisons adjusted using Dunn-Bonferroni methods. Fisher’s exact test was applied to compare the incidence of postoperative adverse events.
Results
Comparison of demographic information
A total of 126 patients were assessed for eligibility; six were excluded, including three who did not meet the inclusion criteria and three who refused to participate. The remaining 120 patients were randomized equally into three groups (Group A, Group B, and Group C). During allocation, three patients in Group B and one in Group C did not receive the allocated intervention due to a change in surgical approach. In the follow-up period, one patient in Group A, three patients in Group B, and one patient in Group C were lost to follow-up because they stayed in the ICU after the operation. Ultimately, 111 patients were included in the final analysis: 39 in Group A, 34 in Group B, and 38 in Group C. The process of patient enrollment, allocation, follow-up, and analysis is detailed in the CONSORT flow diagram (Fig. 1).
Fig. 1.
Consolidated standards of reporting trials flow diagram
The baseline characteristics of the 111 patients were comparable among the three groups (Table 1). No significant differences were observed in gender distribution (P = 0.080), age (P = 0.185), BMI (P = 0.363), operation time (P = 0.600), blood loss (P = 0.551), types of operation (P = 0.176) or length of hospital stay (P = 0.675). ASA classifications were also similar across groups (P = 0.844). These results indicate balanced baseline characteristics among the groups, supporting the validity of subsequent comparisons.
Table 1.
Baseline characteristics by hydromorphone concentration in PCA for laparoscopic postoperative analgesia (N = 111)
| Group A(n = 39) | Group B(n = 34) | Group C(n = 38) | P-Value | |
|---|---|---|---|---|
| Female/Male | 20/19 | 14/20 | 10/28 | 0.080 |
|
Age (years) BMI (kg/m2) Operation time (min) Blood Loss (ml) |
62.4 ± 10.2 23.6 ± 3.8 217.1 ± 94.5 83.3 ± 115.8 |
58.2 ± 10.1 24.4 ± 3.4 229.5 ± 105.5 105.0 ± 120.0 |
60.9 ± 9.4 23.2 ± 3.2 206.6 ± 86.4 111.6 ± 119.1 |
0.185 0.363 0.600 0.551 |
| Types of Operation | 0.176 | |||
| Stomach | 26 | 18 | 17 | |
| Liver | 11 | 13 | 18 | |
| Pancreas | 2 | 3 | 3 | |
| In-hospital days (day) | 7.6 ± 3.3 | 8.3 ± 3.6 | 8.0 ± 3.7 | 0.675 |
| ASA classification (n) | 0.844 | |||
| I | 6 | 7 | 7 | |
| II | 33 | 27 | 31 |
Abbreviation: BMI, body mass index, ASA, American Society of Anesthesiologists.
Primary outcome
The comparisons of VAS scores at rest (VAS-R) and during activity (VAS-A) at 24 h postoperatively are presented in Table 2. There were no significant differences in VAS-R and VAS-A at 24 h among the three groups.
Table 2.
VAS pain scores 24 h after surgery for three groups
| Group A (n = 39) |
Group B (n = 34) |
Group C(n = 38) | P-Value | |
|---|---|---|---|---|
| VAS-R | 0.62 ± 0.71 | 0.82 ± 0.94 | 0.84 ± 1.03 | 0.698 |
| VAS-A | 2.33 ± 1.62 | 2.62 ± 1.33 | 2.76 ± 1.51 | 0.186 |
The Kruskal-Wallis test was used for the Visual Analogue Scale (VAS) score.
Values are expressed as means ± SDs.
Abbreviations: VAS-R, VAS scores at rest, VAS-A, VAS scores during activity.
Secondary outcomes
The comparisons of VAS scores at rest (VAS-R) and during activity (VAS-A) at PACU, 4, 8, and 12 h postoperatively are presented in Table 3. There were no significant differences in VAS-R scores among the three groups at any time point (PACU: P = 0.163; 4 h: P = 0.407; 8 h: P = 0.088; 12 h: P = 0.706). Similarly, VAS-A scores at PACU (P = 0.938), 4 h (P = 0.733), 8 h (P = 0.306), and 12 h (P = 0.302) showed no statistically significant differences among the groups.
Bolus administration frequency differed significantly among the groups (P = 0.002), with Group A utilizing significantly more boluses compared to Groups B and C (Table 4). No significant differences emerged regarding total hydromorphone consumption, catheter removal time, recovery parameters, or vital signs (Figs. 2, 3, 4 and 5). No significant differences were observed among the three groups regarding the incidence of PONV, pruritus, or dizziness (all P > 0.05, Table 5). No cases of respiratory depression occurred in any group.
Fig. 2.
Heart Rate (HR) trends among three groups at different postoperative time points (T0 to T4)
Table 3.
VAS pain scores pacu, 4, 8, 12 h after surgery for three groups
| Group A (n = 39) |
Group B (n = 34) |
Group C(n = 38) | P-Value | |
|---|---|---|---|---|
| VAS-R | ||||
| PACU | 1.21 ± 0.80 | 1.03 ± 0.87 | 0.84 ± 0.74 | 0.163 |
| 4 h | 1.03 ± 0.74 | 0.97 ± 1.09 | 0.79 ± 0.66 | 0.407 |
| 8 h | 0.85 ± 0.81 | 1.21 ± 0.83 | 0.68 ± 0.74 | 0.088 |
| 12 h | 0.77 ± 1.01 | 0.82 ± 0.94 | 0.66 ± 1.03 | 0.706 |
| VAS-A | ||||
| PACU | 2.00 ± 1.48 | 2.50 ± 1.28 | 3.00 ± 1.54 | 0.938 |
| 4 h | 2.59 ± 1.47 | 2.41 ± 1.46 | 2.55 ± 1.39 | 0.733 |
| 8 h | 2.56 ± 1.46 | 2.76 ± 1.18 | 2.61 ± 1.33 | 0.306 |
| 12 h | 2.33 ± 1.46 | 2.59 ± 1.35 | 2.55 ± 1.12 | 0.302 |
The Kruskal-Wallis test was used for the Visual Analogue Scale (VAS) score. Values are expressed as means ± SDs. Abbreviations: VAS-R, VAS scores at rest, VAS-A, VAS scores during activity
Table 4.
Comparison of other secondary outcomes
| Group A (n = 39) |
Group B (n = 34) |
Group C (n = 38) |
P-Value | ||
|---|---|---|---|---|---|
| Bolus frequency | 15.3 ± 13.0 | 10.8 ± 8.3 | 9.7 ± 9.1 | 0.002* | |
| Total hydromorphone consumption(ml) | 29.8 ± 20.1 | 25.4 ± 17.8 | 31.6 ± 23.5 | 0.145 | |
| Catheter removal (days) | 1.7 ± 1.2 | 1.6 ± 1.1 | 1.5 ± 1.0 | 0.682 | |
| Time to first flatus (days) | 2.6 ± 1.7 | 2.8 ± 1.8 | 2.7 ± 1.6 | 0.213 | |
| Time to first feeding (days) | 3.2 ± 2.4 | 2.9 ± 2.1 | 2.7 ± 1.8 | 0.325 | |
| Time to first ambulation (days) | 1.4 ± 0.8 | 1.5 ± 1.1 | 1.3 ± 0.7 | 0.089 | |
Continuous variables were analyzed using the Kruskal-Wallis H test, and pairwise comparisons for significantly different indicators (Bolus frequency) were performed using Dunn-Bonferroni correction. Values are expressed as means ± SDs
Table 5.
Postoperative adverse events
| Group A (n = 39) |
Group B (n = 34) |
Group C (n = 38) |
P-Value | |
|---|---|---|---|---|
| 10 (25.6%) | 8 (23.5%) | 14 (36.8%) | ||
| PONV | 7 (17.9%) | 5 (14.7%) | 9 (23.7%) | 0.613 |
| Pruritus | 2 (5.1%) | 1 (2.94%) | 3 (7.9%) | 0.647 |
| Dizzy | 1 (2.6%) | 1 (2.94%) | 2 (5.3%) | 0.792 |
| Respiratory depression | 0 | 0 | 0 | NA |
Fisher’s exact test was applied to compare the incidence of postoperative adverse events. Values are expressed as number (percentage, %). Abbreviations: PONV, postoperative nausea and vomiting
Fig. 3.
MAP trends among three groups at different postoperative time points (T0 to T4)
Fig. 4.
Respiratory Rate (RR) trends among three groups at different postoperative time points (T0 to T4)
Fig. 5.
Oxygen Saturation (SpO2) Trends Among Three Groups at Different Postoperative Time Points (T0 to T4)
Discussion
In this randomized controlled trial, we evaluated the analgesic efficacy and safety profiles associated with three different hydromorphone bolus doses (0.2 mg, 0.25 mg, and 0.30 mg) administered via patient-controlled intravenous analgesia (PCIA) in patients undergoing laparoscopic surgery. Our findings demonstrated that all three bolus doses provided comparable analgesic efficacy, as evidenced by similar resting and active Visual Analogue Scale (VAS) scores across all assessed postoperative time points (PACU, 4, 8, 12, and 24 h). However, significant differences were noted in bolus administration frequency, with patients receiving the lowest bolus dose (0.20 mg, Group A) requiring more frequent analgesic administration compared to the higher-dose groups.
Optimal postoperative analgesia should achieve adequate pain control, minimize opioid consumption, and reduce adverse events, ultimately facilitating rapid patient recovery and improved satisfaction [19, 20]. While hydromorphone is widely employed in PCIA due to its rapid onset, potent analgesia, and favorable pharmacokinetics [21–23], the ideal bolus dose remains uncertain, especially in laparoscopic surgical populations [24, 25]. Our study contributes valuable data to this clinical question, indicating that increasing hydromorphone bolus doses from 2.0 to 3.0 mL did not significantly enhance analgesic efficacy, as reflected by comparable VAS scores at rest and during activity. Despite a non-significant trend toward lower resting VAS scores in Group C (0.30 mg) at PACU and 8 h postoperatively, these differences did not reach statistical significance, suggesting limited clinical relevance.
Importantly, bolus frequency differed significantly among groups, with Group A (0.20 mg) requiring a notably higher frequency of bolus administrations. This finding aligns with previous observations suggesting that lower opioid bolus doses necessitate more frequent patient-initiated analgesic requests to achieve adequate pain relief, potentially affecting patient convenience and satisfaction [26, 27].
Interestingly, total cumulative hydromorphone consumption did not differ significantly among the three groups. This observation suggests that patients receiving lower bolus doses compensated by increasing the frequency of self-administration, ultimately achieving similar cumulative analgesic consumption. This phenomenon has also been reported previously, emphasizing that total opioid consumption may remain stable across different PCA bolus dosing regimens [28].
Despite differences in administration frequency, total hydromorphone consumption over 24 h was similar between groups. This suggests that patients self-titrate their analgesia, achieving comparable cumulative opioid exposure regardless of bolus size or frequency. Notably, the incidence of opioid-related adverse events, such as postoperative nausea and vomiting (PONV), pruritus, and dizziness, was lowest in the group receiving the intermediate bolus dose of 0.25 mg. Although the total opioid consumption was similar across all groups, the distribution of adverse events suggests that the individual bolus dose may play a more pivotal role than the cumulative dose in determining the risk of opioid-related side effects. This observation is supported by previous studies, which have demonstrated that larger bolus doses can result in higher peak plasma concentrations, thereby increasing the likelihood of adverse events, even when the total opioid exposure remains unchanged [12, 29–32]. While the differences observed in our study did not reach statistical significance, the emerging trend has clinically important implications, given that minimizing opioid-related side effects is a key objective in postoperative pain management.
Recovery parameters, including catheter removal time, time to first flatus, oral intake, and ambulation, were comparable among the three groups, indicating that varying hydromorphone bolus doses within the studied range had minimal impact on postoperative recovery milestones. Vital signs (oxygen saturation, MAP, heart rate, respiratory rate) were also similar across groups, further supporting the safety and clinical acceptability of all three dosing regimens.
Several limitations should be acknowledged. First, this study focused exclusively on laparoscopic procedures and patients classified as ASA I–II, limiting the generalizability of our findings to other surgical populations or higher-risk patient cohorts. Second, the sample size was calculated primarily based on resting VAS scores, possibly limiting statistical power to detect subtle differences in secondary outcomes, particularly adverse events. Finally, the relatively short follow-up period (24 h postoperatively) may not fully capture delayed analgesic effects or late-onset complications associated with different hydromorphone doses.
Conclusion
This study demonstrated that hydromorphone PCIA at bolus doses of 0.20 mg, 0.25 mg, and 0.30 mg provided comparable analgesic efficacy after laparoscopic surgery, as measured by VAS scores. The 0.20 mg dose was associated with increased bolus frequency, while the 0.25 mg dose showed the lowest incidence of adverse events, indicating an optimal balance between pain relief and safety. These findings suggest that a 0.25 mg bolus dose may be preferable for hydromorphone PCIA, though further studies are needed for confirmation.
Supplementary Information
Below is the link to the electronic supplementary material.
Acknowledgements
Not applicable.
Abbreviations
- BMI
body mass index
- ASA
American Society of Anesthesiologists
- PCIA
patient-controlled intravenous analgesia
- VAS
visual analog scale
- VAS-R
VAS scores at rest
- VAS-A
VAS scores during activity
- PACU
post-anesthesia care unit
- MAP
mean arterial pressure
- ERAS
enhanced recovery after surgery
- PONV
postoperative nausea and vomiting
Author contributions
ChunYan Yan conceived and design the study, XinLong Li wrote the main manuscript text, MinJun Liu analyzed the data and prepared all tables and figures, GangChen performed the anesthesia. All authors reviewed the manuscript.
Funding
No funding
Data availability
The datasets generated and/or analysed during the current study are not publicly available due to privacy but available from the corresponding author on reasonable request.
Declarations
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
References
- 1.Liu C, et al. Effect of multimodal preemptive analgesia on postoperative Gastrointestinal function and clinical outcome in patients undergoing laparoscopic colorectal surgery. Int J Clin Pract. 2021;75(12):e14881. [DOI] [PubMed] [Google Scholar]
- 2.Leissner KB, et al. Enhanced recovery after surgery in laparoscopic surgery. J Laparoendosc Adv Surg Tech A. 2017;27(9):883–91. [DOI] [PubMed] [Google Scholar]
- 3.Ren Y, et al. A full enhanced recovery after surgery program in gynecologic laparoscopic procedures: A randomized controlled trial. J Minim Invasive Gynecol. 2021;28(9):1610-e16176. [DOI] [PubMed] [Google Scholar]
- 4.Gan TJ, et al. Incidence, patient satisfaction, and perceptions of post-surgical pain: results from a US National survey. Curr Med Res Opin. 2014;30(1):149–60. [DOI] [PubMed] [Google Scholar]
- 5.Chou R, et al. Management of postoperative pain: A clinical practice guideline from the American pain society, the American society of regional anesthesia and pain medicine, and the American society of anesthesiologists’ committee on regional anesthesia, executive committee, and administrative Council. J Pain. 2016;17(2):131–57. [DOI] [PubMed] [Google Scholar]
- 6.McNicol ED, Ferguson MC, Hudcova J. Patient controlled opioid analgesia versus non-patient controlled opioid analgesia for postoperative pain. Cochrane Database Syst Rev, 2015. 2015(6): p. Cd003348. [DOI] [PMC free article] [PubMed]
- 7.Angster R, Hainsch-Müller I. Postoperative pain management. Anaesthesist. 2005;54(5):505–31. [DOI] [PubMed] [Google Scholar]
- 8.Salicath JH, Yeoh EC, Bennett MH. Epidural analgesia versus patient-controlled intravenous analgesia for pain following intra-abdominal surgery in adults. Cochrane Database Syst Rev. 2018;8(8):Cd010434. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Felden L, et al. Comparative clinical effects of hydromorphone and morphine: a meta-analysis. Br J Anaesth. 2011;107(3):319–28. [DOI] [PubMed] [Google Scholar]
- 10.Murray A, Hagen NA, Hydromorphone. J Pain Symptom Manage. 2005;29(5 Suppl):S57–66. [DOI] [PubMed]
- 11.Yang Y, et al. Prospective investigation of intravenous patient-controlled analgesia with hydromorphone or sufentanil: impact on mood, opioid adverse effects, and recovery. BMC Anesthesiol. 2018;18(1):37. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Hudcova J et al. Patient controlled opioid analgesia versus conventional opioid analgesia for postoperative pain. Cochrane Database Syst Rev, 2006(4): p. Cd003348. [DOI] [PubMed]
- 13.Nie ZB, et al. Hydromorphone vs sufentanil in patient-controlled analgesia for postoperative pain management: A meta-analysis. Med (Baltim). 2022;101(3):e28615. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Gao Y, et al. Patient-controlled intravenous analgesia with combination of Dexmedetomidine and sufentanil on patients after abdominal operation: A prospective, randomized, controlled, blinded, multicenter clinical study. Clin J Pain. 2018;34(2):155–61. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Bernard JM, et al. Patient-controlled epidural analgesia during labor: the effects of the increase in bolus and lockout interval. Anesth Analg. 2000;90(2):328–32. [DOI] [PubMed] [Google Scholar]
- 16.Epsztein Kanczuk M, et al. Programmed intermittent epidural bolus for labor analgesia during first stage of labor: A Biased-Coin Up-and-Down sequential allocation trial to determine the optimum interval time between boluses of a fixed volume of 10 mL of bupivacaine 0.0625% with Fentanyl 2 µg/mL. Anesth Analg. 2017;124(2):537–41. [DOI] [PubMed] [Google Scholar]
- 17.Gambling DR, et al. Patient-controlled epidural analgesia in labour: varying bolus dose and lockout interval. Can J Anaesth. 1993;40(3):211–7. [DOI] [PubMed] [Google Scholar]
- 18.Srikandarajah S, Gilron I. Systematic review of movement-evoked pain versus pain at rest in postsurgical clinical trials and meta-analyses: a fundamental distinction requiring standardized measurement. Pain. 2011;152(8):1734–9. [DOI] [PubMed] [Google Scholar]
- 19.Cheung CK, et al. Postoperative pain management in enhanced recovery pathways. J Pain Res. 2022;15:123–35. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.White PF, et al. The role of the anesthesiologist in fast-track surgery: from multimodal analgesia to perioperative medical care. Anesth Analg. 2007;104(6):1380–96 table of contents. [DOI] [PubMed] [Google Scholar]
- 21.Wang L, et al. Ketamine added to morphine or hydromorphone patient-controlled analgesia for acute postoperative pain in adults: a systematic review and meta-analysis of randomized trials. Can J Anaesth. 2016;63(3):311–25. [DOI] [PubMed] [Google Scholar]
- 22.Alinejadfard M, et al. Efficacy and safety of hydromorphone for cancer pain: a systematic review and meta-analysis. BMC Anesthesiol. 2024;24(1):283. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Li Y, et al. Effectiveness and safety of hydromorphone compared to morphine for postoperative analgesia: A systematic review and Meta-analysis. Pain Physician. 2024;27(8):469–78. [PubMed] [Google Scholar]
- 24.Lee W, et al. Postoperative sufentanil intravenous patient-controlled analgesia within the first 24 hours: a retrospective study. Ann Palliat Med. 2020;9(6):3932–7. [DOI] [PubMed] [Google Scholar]
- 25.Ma Y, et al. Effects of hydromorphone-based patient-controlled intravenous analgesia on postoperative hypoxaemia: a randomised controlled non-inferiority clinical trial. BMJ Open. 2024;14(7):e084827. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Bai Y, et al. Postoperative analgesic effect of hydromorphone in patients undergoing single-port video-assisted thoracoscopic surgery: a randomized controlled trial. J Pain Res. 2019;12:1091–101. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Huang CY, et al. A comparative study of three concentrations of intravenous Nalbuphine combined with hydromorphone for post-cesarean delivery analgesia. Chin Med J (Engl). 2020;133(5):523–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Wehrfritz A, et al. Postoperative pain therapy with hydromorphone; comparison of patient-controlled analgesia with target-controlled infusion and standard patient-controlled analgesia: a randomised controlled trial. Eur J Anaesthesiol. 2020;37(12):1168–75. [DOI] [PubMed] [Google Scholar]
- 29.Grass JA. Patient-controlled analgesia. Anesth Analg. 2005;101(5):S44-61. [DOI] [PubMed] [Google Scholar]
- 30.Chang AK, et al. Randomized clinical trial of the 2 mg hydromorphone bolus protocol versus the 1 + 1 hydromorphone Titration protocol in treatment of acute, severe pain in the first hour of emergency department presentation. Ann Emerg Med. 2013;62(4):304–10. [DOI] [PubMed] [Google Scholar]
- 31.Coda B, et al. Hydromorphone analgesia after intravenous bolus administration. Pain. 1997;71(1):41–8. [DOI] [PubMed] [Google Scholar]
- 32.Egan TD, et al. Remifentanil by bolus injection: a safety, pharmacokinetic, pharmacodynamic, and age effect investigation in human volunteers. Br J Anaesth. 2004;92(3):335–43. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The datasets generated and/or analysed during the current study are not publicly available due to privacy but available from the corresponding author on reasonable request.