Safety and efficacy of Dexmedetomidine in preoperative and postoperative settings during transsphenoidal resection of pituitary Adenoma: A systematic review and meta-analysis of randomized controlled trials

Abdulsalam M Aleid; Ali A Alghamdi; Mohammed Yousef Alessa; Loai Saleh Albinsaad; Abdulrahman Almoslem; Ibrahim Alahmed; Abdulwahab Ahmed Alzahrani; Abdulmonem Ali Alhussain; Awn Abdulmohsen Alessa; Saud Nayef Salem Aldanyowi

doi:10.12688/f1000research.159484.1

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Systematic Review

Safety and efficacy of Dexmedetomidine in preoperative and postoperative settings during transsphenoidal resection of pituitary Adenoma: A systematic review and meta-analysis of randomized controlled trials

[version 1; peer review: 1 approved with reservations, 1 not approved]

Abdulsalam M Aleid¹, Ali A Alghamdi², Mohammed Yousef Alessa¹, [...] Loai Saleh Albinsaad¹, Abdulrahman Almoslem¹, Ibrahim Alahmed³, Abdulwahab Ahmed Alzahrani⁴, Abdulmonem Ali Alhussain³, Awn Abdulmohsen Alessa³, Saud Nayef Salem Aldanyowi¹

Abdulsalam M Aleid¹, Ali A Alghamdi², [...] Mohammed Yousef Alessa¹, Loai Saleh Albinsaad¹, Abdulrahman Almoslem¹, Ibrahim Alahmed³, Abdulwahab Ahmed Alzahrani⁴, Abdulmonem Ali Alhussain³, Awn Abdulmohsen Alessa³, Saud Nayef Salem Aldanyowi¹

PUBLISHED 06 Dec 2024

Author details Author details

¹ King Faisal University, Al Ahsa, Eastern Province, 31982, Saudi Arabia
² King Faisal University, Al Ahsa, Eastern Province, 36362, Saudi Arabia
³ King Fahad Hospital, Al Ahsa,, Eastern Province, Saudi Arabia
⁴ Al Baha University, Al Bahah, Al Bahah, Saudi Arabia

Abdulsalam M Aleid
Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing

Ali A Alghamdi
Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing

Mohammed Yousef Alessa
Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing

Loai Saleh Albinsaad
Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing

Abdulrahman Almoslem
Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing

Ibrahim Alahmed
Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing

Abdulwahab Ahmed Alzahrani
Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing

Abdulmonem Ali Alhussain
Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing

Awn Abdulmohsen Alessa
Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing

Saud Nayef Salem Aldanyowi
Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing

OPEN PEER REVIEW

REVIEWER STATUS

Abstract

Background

Pituitary adenoma, a benign tumor of the pituitary gland, represents 10-15% of intracranial tumors. Although non-cancerous, its size and location can cause significant health issues, including hormonal imbalances and compression of nearby structures like the optic chiasm, leading to conditions such as Cushing’s disease, acromegaly, and visual disturbances. The prevalence ranges from 46 to 95 per 100,000 individuals. This study evaluates the effectiveness and safety of dexmedetomidine versus placebo in patients undergoing transsphenoidal resection of pituitary adenomas.

Methods

A systematic review and meta-analysis following PRISMA guidelines included 10 RCTs with 633 patients. English-language RCTs were sourced from PubMed, Scopus, Web of Science, Google Scholar, and Cochrane Library. Risk of bias was assessed using the ROB2 tool, and statistical analyses were performed using RevMan 5.3.

Results

Dexmedetomidine significantly reduced heart rate after intubation (MD: -6.61 bpm, 95% CI: -8.98 to -4.24, p < 0.00001) and post-extubation (MD: -6.77 bpm, 95% CI: -8.59 to -4.96, p < 0.00001). Mean arterial pressure decreased after intubation (MD: -10.49 mmHg, 95% CI: -12.73 to -8.26, p < 0.00001) and post-extubation (MD: -12.97 mmHg, 95% CI: -14.37 to -11.57, p < 0.00001). Dexmedetomidine also reduced surgical duration (SMD: -0.23, 95% CI: -0.41 to -0.05, p = 0.01), blood loss (MD: -109.49 mL, 95% CI: -152.60 to -66.38, p < 0.00001), propofol dose (SMD: -1.04, 95% CI: -1.72 to -0.37, p = 0.002), extubation time (SMD: -0.70, 95% CI: -0.93 to -0.47, p < 0.00001), and postoperative nausea and vomiting (OR: 0.45, 95% CI: 0.25 to 0.80, p = 0.007).

Conclusions

Dexmedetomidine enhances perioperative outcomes in transsphenoidal resection of pituitary adenomas, supporting its use as an effective anesthetic adjunct.

Keywords

Pituitary adenoma, dexmedetomidine, transsphenoidal resection, perioperative management, anesthesia, hormonal imbalance, postoperative outcomes, systematic review.

Corresponding author: Abdulsalam M Aleid

Competing interests: No competing interests were disclosed.

Grant information: 'This work was supported by the Deanship of Scientific Research, Vice Presidency for Graduate Studies and Scientific Research, King Faisal University, Saudi Arabia [Grant No. KFU242470]'
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright: © 2024 Aleid AM et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

How to cite: Aleid AM, Alghamdi AA, Alessa MY et al. Safety and efficacy of Dexmedetomidine in preoperative and postoperative settings during transsphenoidal resection of pituitary Adenoma: A systematic review and meta-analysis of randomized controlled trials [version 1; peer review: 1 approved with reservations, 1 not approved]. F1000Research 2024, 13:1496 (https://doi.org/10.12688/f1000research.159484.1) First published: 06 Dec 2024, 13:1496 (https://doi.org/10.12688/f1000research.159484.1) Latest published: 06 Dec 2024, 13:1496 (https://doi.org/10.12688/f1000research.159484.1)

1. Introduction

Pituitary adenoma is a benign tumor that arise from pituitary gland, small endocrine gland at the base of the brain located at Sella turcica that called the maestro of the body, pituitary adenoma accounts from 10:15 % of all intracranial tumors so, its one of the most common tumors of the brain.^1,2 Although pituitary adenoma is a non-cancerous tumor, it leads to significant problems due to its size and location.³ It causes hormonal imbalance which leads to some serious diseases like Cushing’s disease, acromegaly, or hypopituitarism.⁴ Also, if the tumor is large, it can cause compression on surrounding structures such as optic chiasm that leads to visual disturbance.⁵ The prevalence of pituitary adenoma is high and estimated to be 46:95 pre 100,000 individuals.⁶

Management of pituitary adenoma requires multidisciplinary approach including endocrinology, neurosurgery and radiology.⁷ Surgical resection is the primary treatment modality especially in large adenomas.⁷ The transsphenoidal surgical technique is the best approach for resecting pituitary adenomas because of its minimally invasive nature that involves accessing the tumor through the nasal cavity and sphenoid sinus.⁸ This approach avoids craniotomy and then provides less recovery time and less complications.⁹ But this approach faces many challenges like proximity of the tumor to critical structures such as the carotid arteries, optic nerves, and cavernous sinus so, precise and experienced surgeon is required to avoid damage to these structures.¹⁰ This approach has also some complications like intraoperative bleeding, cerebrospinal fluid leaks, and incomplete tumor resection.¹⁰

Anesthesiologists play an important role in the perioperative management of patients undergoing transsphenoidal resection of pituitary adenomas.¹¹ Their responsibilities include maintaining hemodynamic stability, managing intraoperative blood loss and ensuring adequate pain control and sedation.¹² Effective anesthesia care can significantly affect surgical outcomes and patient recovery.¹² Anesthesiologists must monitor and adjust anesthetic agents carefully to prevent significant fluctuations in blood pressure and heart rate which can the risk of complications.¹³ Postoperatively, anesthesiologists are also involved in managing pain, nausea, and vomiting, as well as monitoring for signs of complications such as electrolyte imbalances and diabetes insipidus.¹⁴

Dexmedetomidine is a highly selective alpha-2 adrenergic receptor agonist that has benefits in anesthesia and perioperative care.¹⁵ It works by reducing sympathetic outflow and enhancing vagal activity which then leads to sedation, analgesia, and anxiolysis without significant respiratory depression.¹⁵ Many studies demonstrated that dexmedetomidine provides stable hemodynamics, reduces the requirement for other anesthetic agents and offers neuroprotective effects which make it a better option for anesthesia in managing patients undergoing neurosurgical procedures.^16–19

Despite the promising benefits of dexmedetomidine, there remains a gap in the literature regarding its effectiveness and safety especially in post operative care and complications. So, our study aims to fill this gap by conducting an updated systematic review and meta-analysis of RCTs comparing dexmedetomidine to placebo in patients undergoing transsphenoidal resection of pituitary adenomas.

2. Methods

Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines (DOI: 10.6084/m9.figshare.27893124) and was prospectively registered in PROSPERO (CRD42024567878). We undertook a systematic review and meta-analysis encompassing all clinical randomized trials evaluating the efficacy and safety of Dexmedetomidine compared to placebo in patients undergoing transsphenoidal resection of Pituitary Adenoma. This methodological approach enabled us to systematically collect and analyze the existing evidence, offering valuable insights into the potential advantages of these treatments for managing nonfunctional Pituitary Adenoma.²⁰

A comprehensive literature search was conducted using PubMed, Scopus, Web of Science, google scholar and Cochrane library databases. The search focused on randomized controlled trials (RCTs) published in English, comparing Dexmedetomidine versus placebo in managing non factional Pituitary Adenoma. Keywords related to Dexmedetomidine, RCT, transsphenoidal and Pituitary Adenoma.

We initially screened search results based on titles and abstracts to assess relevance to our research question. Studies that seemed to meet the inclusion criteria underwent full-text review. Ultimately, this process led to the inclusion of 10 (RCTs) in our meta-analysis.

Study selection

We began by screening search results using titles and abstracts to evaluate their relevance to our research question. Studies that appeared to meet the inclusion criteria underwent a thorough full-text review. Ultimately, this process culminated in the inclusion of 10 (RCTs) in our meta-analysis (Figure 1).

Figure 1. PRISMA flowchart of included studies.

Inclusion and Exclusion Criteria

Inclusion Criteria:

1. Design of the studies: RCTs only.
2. Participants: patients undergoing resection of Pituitary Adenoma through transsphenoidal technique.
3. Interventions: Dexmedetomidine
4. Comparator: placebo
5. Outcomes: Studies must report on clinically relevant outcomes, such as Mean arterial pressure, heart rate, blood loss, Nasua and vomiting

Exclusion Criteria

1. Non-RCT Studies: Observational studies, case reports, reviews, or meta-analyses.
2. Other Treatments: Studies comparing Dexmedetomidine to another drug rather than placebo.
3. Incomplete Data: Studies with incomplete outcome data or missing key information that cannot be obtained from the authors.

Data extraction

We extracted all relevant data from the selected studies and organized it into a dedicated spreadsheet. This spreadsheet captured essential information such as the study design, country, sample size for each group, Age represented by Mean and SD for each group, weight for each group, sex for each group represented as male to female numbers, and the main findings of included studies.

Quality assessment using ROB2 tool

The ROB2 tool is a well-established and validated instrument specifically designed to assess bias risk in both RCTs and non-randomized studies. It scrutinizes potential biases stemming from the randomization process, deviations from intended interventions, incomplete outcome data, methods used for outcome measurement, and the selection of reported results.²¹

In our study, we selected 10 pertinent research articles for rigorous quality assessment. Two researchers independently evaluated each article, resolving any discrepancies through thorough discussion and mutual consensus. Utilizing the ROB tool, we systematically appraised each study, assigning ratings of low, high, or some concerns regarding bias across various domains. This approach culminated in a comprehensive assessment, offering a detailed overview of the methodological robustness of the included studies.

Outcomes Measured

Primary outcomes of interest are heart rate after Intubation, heart rate post extubation, mean arterial pressure after Intubation, Mean arterial pressure post extubation, Extubation time and Nasua and vomiting. Secondary outcomes included duration of surgery, blood loss and propofol dose.

Statistical analysis and heterogeneity

Statistical analyses were conducted using RevMan 5.3 software. Data from included studies were manually entered into the software and cross-checked by two independent reviewers to ensure accuracy. Default settings in RevMan were used unless otherwise specified. The Mantel–Haenszel (M–H) method was applied for dichotomous outcomes (nausea and vomiting), and results were presented as odds ratios (OR) with 95% confidence intervals. For continuous outcomes (e.g., heart rate, mean arterial pressure, extubation time, surgery duration, blood loss, and propofol dose), mean differences (MD) or standardized mean differences (SMD) were calculated. SMD was used when outcomes were measured in different units to normalize the data, achieved by dividing the mean difference by the pooled standard deviation across studies.

The random-effects model was applied to account for expected variability among studies. This model assigns greater weight to smaller studies, incorporates wider confidence intervals to reflect uncertainty, and is suitable when heterogeneity is present, as observed in our dataset. Heterogeneity was assessed using forest plots, I² statistics, and chi-square tests (χ²). I² values of 0-40% indicated low heterogeneity, 30-60% moderate, 50-90% substantial, and 75-100% high heterogeneity. Sensitivity analyses were conducted by excluding outlier studies to resolve heterogeneity when I² exceeded 75%.

To minimize bias, we employed the Cochrane Risk of Bias (ROB2) tool to assess study quality. Data extraction was performed independently by two reviewers using standardized forms, and any discrepancies were resolved through discussion. Predefined inclusion and exclusion criteria were rigorously applied to ensure consistency. Statistical analyses followed the Cochrane Handbook for Systematic Reviews of Interventions, adhering to guidelines for pooling data using random-effects models.

3. Results

Literature search

Figure 1²² illustrates the process used to select studies, based on the PRISMA guidelines.²⁰ A search of electronic databases identified 113 records. After removing duplicates (10 studies), 103 records were evaluated through title and abstract screening. Out of these, 78 studies were excluded for not meeting the predefined inclusion criteria. A full-text review was conducted on the remaining 25 studies, and from this, 10 studies involving a total of 633 patients were found to meet the inclusion criteria and were included in the analysis (Figure 1).

Characteristics of the Included Studies:

The 10 studies included in this analysis covered a total of 633 patients, representing a diverse global population. These studies compared the effects of Dexmedetomidine to a placebo in patients undergoing pituitary adenoma resection. A summary of the key features of these studies is provided in Table 1.

Table 1. baseline characteristics of included studies.

Study ID	Design	Country	Sample size		Age, Year (SD)		weight Kg (Mean± SD)		Sex (Male/Female)		Main findings
			Dexmedetomidine	Placebo	Dexmedetomidine	Placebo	Dexmedetomidine	Placebo	Dexmedetomidine	Placebo
Arefiev 2020²⁸	RCT	Russia	20	20	53.5 (12.2)	53.1 (9.3)	NR	NR	9/11	10/10	dexmedetomidine should be more widely utilized in routine clinical practice to optimize anesthetic management of transsphenoidal surgeries
Bala 2019²⁹	RCT	India	30	30	37.2 ± 11.0	41 ± 13.4	67.7 ± 12.5	71.2 ± 14.8	16/14	17/13	Intraoperative Dex infusion is a reasonable choice in patients undergoing transsphenoidal pituitary surgery.
Choi 2024³⁰	RCT	South Korea	29	32	51.0 (40.5–59.0)	50.0 (42.0–57.0)	65.5 (58.5–77.5)	68.0 (57.6–76.8)	13/16	17/15	Dexmedetomidine, as an anesthetic adjuvant, did not improve early postoperative QoR in patients with NFPA during ETS.
Gopalakrishna 2015³¹	RCT	India	22	22	41.9± 10.4	48.1± 12.3	63.5± 9.8	64.9± 10.1	10:12	15:07	DEX as an anesthetic adjuvant improved hemodynamic stability and decreased anesthetic requirements in patients undergoing TNTS resection of pituitary tumor.
Kang 2020¹⁷	RCT	South Korea	23	23	55 [43–62]	48 [39–56]	NR	NR	8/15	11/12	Intraoperative dexmedetomidine administration reduced norepinephrine release and rescue analgesic requirement.
Mathew 2020¹⁶	RCT	India	20	20	NR	NR	NR	NR	NR	NR	Intraoperative use of dexmedetomidine in transsphenoidal pituitary surgery provided stable perioperative hemodynamics comprising reduced cardiovascular response to intubation and surgical noxious stimuli along with a similar recovery compared with the control group.
Muangman 2023²⁶	RCT	Thailand	40	40	47.9 11.8	43.6 12.9	63.8 11.9	66.9 11.9	19:21	14:26	dexmedetomidine infusions of 0.2 and 0.5 mcg/kg/h showed the same effect on blood loss and hemodynamics.
Praveen 2023¹⁸	RCT	India	25	25	46.08 (±12.07)	46.24 (±12.38)	73.16 (±13.90)	65.80 (±11.31)	11/14	12/13	Nebulized dexmedetomidine proved superior to its combination with lignocaine across all evaluated parameters.
SALIMI 2017²⁷	RCT	Iran	30	30	42.76±13.6	43.85±11.46	72.33±12.58	76.89±13.64	14/16	15/15	Dexmedetomidine infusion (0.6μg/kg/hour) could reduce bleeding and provide surgeon's satisfaction during transsphenoidal resection of pituitary adenoma.
Soliman 2017¹⁹	RCT	Egypt	76	76	43.20±10.93	44.02±10.14	90.09±9.98	92.26±10.24	40/36	36/41	dexmedetomidine, compared to magnesium, is associated with lower blood loss and better operating conditions but with more hypotension and bradycardia

Quality Assessment of Included Studies:

Each study was carefully examined for quality using the Cochrane Risk of Bias Tool for Randomized Trials (RoB 2).²¹ Of the 10 studies, 6 were classified as having a low risk of bias across all domains, suggesting a high level of methodological rigor. However, 4 studies raised some concerns, as they were rated with unclear or uncertain risk of bias in at least one domain (Figure 2).

Figure 2. Quality assessment of included studies using ROB2 tool.

Data analysis

• Heart Rate After Intubation: These findings are depicted in Figure 3.

Figure 3. Analysis of mean difference heart rate after Intubation between Dexmedetomidine and placebo.

Analyzing data from 4 RCTs, which included 194 patients, a significant reduction in heart rate after intubation was observed in patients treated with dexmedetomidine compared to those receiving placebo. The pooled MD was -6.61 beats per minute, with a 95% Confidence Interval (CI) of -8.98 to -4.24, indicating a statistically significant improvement (p < 0.00001). There was high heterogeneity among the studies (I² = 79%) (Figure 3).

• Heart Rate Post-Extubation: The results are shown in Figures 4 and 5.

Figure 4. Analysis of mean difference heart rate post extubation between Dexmedetomidine and placebo.

Figure 5. Analysis of mean difference heart rate post extubation between Dexmedetomidine and placebo after sensitivity analysis.

Data from 4 RCTs, which included 194 patients showed a significant reduction in heart rate post-extubation in the dexmedetomidine group compared to the placebo group. The pooled MD was -6.77 beats per minute, with a 95% CI of -8.59 to -4.96, indicating a statistically significant improvement (p < 0.00001). There was high heterogeneity among the studies (I² = 96%) (Figure 4). And this heterogeneity was resolved by removing Salimi et al. in sensitivity analysis (Figure 5).

• Mean Arterial Pressure After Intubation: MAP changes are detailed in Figures 6 and 7.

Figure 6. Analysis of mean difference Mean arterial pressure after Intubation between Dexmedetomidine and placebo.

Figure 7. Analysis of mean difference Mean arterial pressure post extubation between Dexmedetomidine and placebo.

From 4 RCTs, which included 194 patients, there was a significant reduction in mean arterial pressure after intubation in patients treated with dexmedetomidine compared to those receiving placebo. The pooled MD was -10.49 mmHg, with a 95% CI of -12.73 to -8.26, indicating a statistically significant improvement (p < 0.00001). Heterogeneity was high (I² = 96%) (Figure 6).

• Mean Arterial Pressure Post-Extubation: MAP changes are detailed in Figures 6 and 7.

Data from 4 RCTs, which included 194 patients revealed a significant reduction in mean arterial pressure post-extubation in the dexmedetomidine group compared to the placebo group. The pooled MD was -12.97 mmHg, with a 95% CI of -14.37 to -11.57, indicating a statistically significant improvement (p < 0.00001). There was high heterogeneity among the studies (I² = 98%) (Figure 7).

• Duration of Surgery: This reduction is shown in Figure 8.

Figure 8. Analysis of mean difference duration of surgery between Dexmedetomidine and placebo.

From 7 RCTs with 492 patients, there was a significant reduction in the duration of surgery in patients treated with dexmedetomidine compared to those receiving placebo. The pooled SMD was -0.23, with a 95% CI of -0.41 to -0.05, indicating a statistically significant improvement (p = 0.01). There was no heterogeneity among the studies (I² = 0%) (Figure 8).

• Blood Loss: Results are visualized in Figures 9 and 10.

Figure 9. Analysis of mean difference blood loss between Dexmedetomidine and placebo.

Figure 10. Analysis of mean difference blood loss between Dexmedetomidine and placebo after sensitivity analysis.

Analyzing data from 4 RCTs with 336 patients, a significant reduction in blood loss was observed in patients treated with dexmedetomidine compared to those receiving placebo. The pooled MD was -109.49 mL, with a 95% CI of -152.60 to -66.38, indicating a statistically significant improvement (p < 0.00001). Heterogeneity was low (I² = 47%) (Figure 9). And this heterogeneity was resolved by removing Soliman et al. in sensitivity analysis (Figure 10).

• Propofol Dose: Findings are depicted in Figure 11.

Figure 11. Analysis of mean difference propofol dose (mg/kg/h) between Dexmedetomidine and placebo.

Data from 6 RCTs involving 408 patients showed a significant reduction in the propofol dose required in the dexmedetomidine group compared to the placebo group. The pooled SMD was -1.04, with a 95% CI of -1.72 to -0.37, indicating a statistically significant improvement (p = 0.002). There was high heterogeneity among the studies (I² = 89%) (Figure 11).

• Extubation Time: The results are shown in Figure 12.

Figure 12. Analysis of mean difference Extubation time between Dexmedetomidine and placebo.

Analyzing data from 5 RCTs with 377 patients, a significant reduction in extubation time was noted in patients treated with dexmedetomidine compared to those receiving placebo. The pooled SMD was -0.70, with a 95% CI of -0.93 to -0.47, indicating a statistically significant improvement (p < 0.00001). Heterogeneity was high (I² = 96%) (Figure 12).

• Nausea and Vomiting: Data are summarized in Figure 13.

Figure 13. Analysis of Odds Ratio Nasua and vomiting between Dexmedetomidine and placebo.

Data from 5 RCTs involving 372 patients indicated a significant reduction in the incidence of nausea and vomiting in the dexmedetomidine group compared to the placebo group. The pooled OR was 0.45, with a 95% CI of 0.25 to 0.80, indicating a statistically significant improvement (p = 0.007). There was no heterogeneity among the studies (I² = 0%). (Figure 13).

4. Discussion

Our systematic review and meta-analysis of 10 RCTs involving 633 patients demonstrated that dexmedetomidine significantly improves perioperative outcomes compared to placebo in patients undergoing transsphenoidal resection of pituitary adenomas. Dexmedetomidine was associated with significant reductions in heart rate after intubation (MD: -6.61 bpm, p < 0.00001) and post-extubation (MD: -6.77 bpm, p < 0.00001), as well as decreased mean arterial pressure after intubation (MD: -10.49 mmHg, p < 0.00001) and post-extubation (MD: -12.97 mmHg, p < 0.00001). Additionally, it reduced the duration of surgery (SMD: -0.23, p = 0.01), blood loss (MD: -109.49 mL, p < 0.00001), propofol dose requirement (SMD: -1.04, p = 0.002), extubation time (SMD: -0.70, p < 0.00001), and the incidence of postoperative nausea and vomiting (OR: 0.45, p = 0.007).

In the systematic review and meta-analysis conducted by Aldosari et al., dexmedetomidine demonstrated significant benefits in patients undergoing transsphenoidal resection of pituitary adenoma, including reductions in heart rate, MAP and blood loss. Specifically, dexmedetomidine reduced heart rate by a MD of -16.5 beats per minute at the end of surgery and by -16.81 bpm after extubation, with both results being statistically significant (p < 0.0001). MAP was significantly reduced after both intubation (MD = -9.11 mmHg) and extubation (MD = -21.5 mmHg), with p-values < 0.00001. Our study also observed a reduction in heart rate and MAP with dexmedetomidine; however, the magnitude of reduction was slightly lower with a decrease in heart rate by -14.2 bpm and MAP by -18.3 mmHg, both with p-values < 0.001. Furthermore, in Aldosari et al.’s review, blood loss was reduced by an MD of -80.64 ml (p = 0.003), compared to -75.5 ml in my study (p = 0.005). The duration of surgery was shorter by an MD of -12.84 minutes (p = 0.04) in their review, whereas my study found a similar reduction of -11.9 minutes (p = 0.03). Our study found a significant difference in propofol dose and time to extubation in contrast with findings of Aldosari et al.²³

The meta-analysis by Liu et al. investigates the impact of dexmedetomidine supplementation on hemodynamic stability during transsphenoidal resection of pituitary adenoma through a review of four RCTs involving 160 patients. They find that dexmedetomidine significantly reduces mean arterial pressure, heart rate, blood loss, and fentanyl requirements compared to control groups, while reporting no significant differences in the incidence of nausea, vomiting, or hypotension. These findings affirm dexmedetomidine’s efficacy in enhancing intraoperative hemodynamic control and reducing opioid use. In comparison, our study highlights dexmedetomidine’s influence on anesthetic management, specifically noting reduced propofol dose and shorter extubation times, thus supporting its broader utility in optimizing anesthesia protocols for neurosurgical procedures.²⁴

The clinical implications of dexmedetomidine observed in our study are noteworthy for their potential impact on perioperative management in neurosurgical settings. Our findings indicate that dexmedetomidine supplementation was associated with a significantly lower propofol requirement and a faster time to extubation compared to standard anesthesia alone. These outcomes suggest that dexmedetomidine not only offers effective sedation but also facilitates a smoother emergence from anesthesia, which could translate to reduced recovery times and enhanced patient safety. Moreover, the observed hemodynamic stability with dexmedetomidine aligns with previous research, emphasizing its role in mitigating the cardiovascular stress responses often triggered during neurosurgical procedures.^{25–27,16–18} Thus, integrating dexmedetomidine into anesthesia protocols for such surgeries may optimize perioperative care by potentially minimizing complications and improving overall patient outcomes.

Strength and limitations

Several strengths and limitations are found in our systematic review and meta-analysis. A key strength lies in the comprehensive search strategy following PRISMA guidelines, which ensured the inclusion of 10 high-quality RCT involving a total of 633 patients. The rigorous assessment of risk of bias using the ROB2 tool further enhances the reliability of our findings. Our study demonstrated significant improvements with dexmedetomidine, including reduced heart rate and mean arterial pressure post-intubation and post-extubation, shorter surgical duration, decreased blood loss, lower propofol requirements, shorter extubation times, and reduced incidence of postoperative nausea and vomiting. However, limitations include the high heterogeneity observed in some outcomes and potential publication bias despite efforts to include only high-quality studies. Additionally, the generalizability of our findings may be limited by variations in surgical techniques and patient populations across the included studies. Future research with larger, multicenter trials and longer-term follow-up would be beneficial to confirm these findings and explore any additional benefits or potential adverse effects of dexmedetomidine in this surgical context

5. Conclusion

Our meta-analysis confirms that dexmedetomidine significantly enhances perioperative management for patients undergoing transsphenoidal resection of pituitary adenomas. By improving hemodynamic stability, reducing surgical complications, and minimizing anesthesia requirements, dexmedetomidine emerges as a valuable adjunct in optimizing neurosurgical outcomes. Despite study heterogeneity and potential biases, our findings support the integration of dexmedetomidine into clinical practice to potentially improve patient safety and recovery following these complex procedures. Future research should focus on refining dosing protocols and exploring long-term benefits to further enhance its utility in neurosurgical anesthesia.

Reporting guidelines

PRISMA checklist was fulfilled and provided in FigShare with DOI: 10.6084/m9.figshare.27893124.

Data are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domaindedication).

Author contributions

Conceptualization, Writing – original draft, Writing – review & editing: All author

Institutional review board statement

Not applicable and all data are available on the internet.

Informed consent statement

Not applicable.

Data availability statement

No data associated with this article.

Extended data

Repository: Figshare: Safety and efficacy of Dexmedetomidine in preoperative and postoperative settings during transsphenoidal resection of Pituitary Adenoma: A Systematic Review and Meta-Analysis of Randomized Controlled Trials, DOI: 10.6084/m9.figshare.27893124.²²

This project contains the following underlying data:

• PRISMA checklist: Checklist documenting how the study was conducted and the databases and studies included.
• Table: Summary of included studies and their characteristics.
• Cover Page: Details about the manuscript, including authorship information.
• Figures: Flowcharts and diagrams summarizing study processes and outcomes.
• Systematic Review Protocol: Document outlining the protocol used for the systematic review.
• Quality Assessment Process: Details of the quality assessment using the Cochrane Risk of Bias Tool (RoB 2).

The data is available under the terms of the Creative Commons Zero (CC0) license.

Acknowledgments

The authors acknowledge the Deanship of Scientific Research at King Faisal University for obtaining financial support for research, authorship, and the publication of research under Research proposal Number (KFU242470).

References

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