ABSTRACT

Background:

Propofol is a cornerstone of modern anaesthesia. Despite extensive research, the landmark studies shaping its clinical use remain unmapped. This study aimed to identify and analyse the top 50 most-cited articles on propofol in anaesthesia to highlight evolutionary trends and influential contributions.  

Methods:

A bibliometric analysis was conducted using Web of Science with the keywords “propofol” and “anaesthesia.” Articles were screened for relevance to efficacy and safety. The top 50 articles were selected based on citation count. Data on citations, metrics, geography, and study design were extracted and analysed descriptively.

Results:

The 50 papers accumulated 5,252 citations (mean = 104.1). Randomised controlled trials predominated (46%), while systematic reviews were limited (8%). Geographically, 66% of the publications originated from Europe, indicating a significant regional concentration.

Conclusion:

This analysis confirms propofol’s central role in anaesthesia while revealing critical gaps in data synthesis and global representation. The reliance on European-centric data limits universal applicability. Future research should focus on multinational collaborations and high-quality systematic reviews to establish globally diverse and safer induction protocols.

Keywords:

Propofol, anesthesia, induction, bibliometric analysis.

Introduction

Anaesthesia plays a crucial role in reducing pain and anxiety. Among the available techniques, intravenous general anaesthesia is widely preferred due to its rapid onset, precise control over the depth of sedation, and minimal residual effects [1]. Propofol is an intravenous anesthetic widely used for the induction and maintenance of general anaesthesia, total intravenous anaesthesia, procedural sedation, and intensive care unit sedation [2].

It is a short-acting agent with a favorable induction profile, rapid clearance, and swift penetration of the blood–brain barrier. These characteristics allow for rapid onset and recovery. Pharmacologically, propofol exhibits strong sedative, hypnotic, and anxiolytic effects, but minimal analgesic activity [3-5].

The exact mechanism of action of propofol remains unclear; however, it is primarily attributed to positive allosteric modulation of gamma-aminobutyric acid type A receptors, enhancing inhibitory neurotransmission in the central nervous system. Additional laboratory evidence suggests potential anti-inflammatory and antioxidant effects [6].

The effectiveness and safety profile of propofol-induced sedation are well documented [7-9]. However, its use is associated with adverse effects such as apnea, cardiovascular depression, injection pain, and, rarely, infusion syndrome, highlighting the need for safer alternatives with comparable benefits [10-12].

Although extensive research has clarified its pharmacology, efficacy, and adverse effects, limited efforts have been made to consolidate the most highly cited studies guiding clinical practice and innovation in anaesthesia induction. Furthermore, bibliometric analyses remain limited in addressing emerging trends such as safety evaluation, development of novel analogues, electroencephalography (EEG) guided dosing approaches, and real-world effectiveness across diverse populations.

In regional and national anaesthesia literature, including several high-impact studies conducted in Saudi Arabia, comparisons among different commercial propofol formulations have demonstrated equivalent induction quality when assessed using the bispectral index (BIS) and hemodynamic parameters, while highlighting cost as a key determinant in clinical decision-making [13].

To the best of our knowledge, no previous study has analysed the top 50 most cited articles on propofol use in anaesthesia induction with respect to efficacy, safety, and innovation. Therefore, this study was undertaken to address this gap. This study aims to evaluate the characteristics and quality of the top 50 cited articles, focusing on efficacy, safety, and innovation, while identifying emerging research trends in the field.

Methods

Search strategy and study selection

A comprehensive literature search was conducted using the Web of Science Core Collection database, which is well recognised for its robust citation indexing and suitability for bibliometric analyses [14].

As shown in Figure 1, the search initially retrieved 1,036 records. The keywords “propofol” and “anaesthesia” were used in combination with Boolean operators to identify relevant publications, with no restrictions applied regarding the year of publication to ensure comprehensive coverage of the literature. Citation analysis was conducted by ranking Web of Science records according to total citation counts, and a citation-based filtering approach was used to identify the 100 most-cited records for screening, consistent with established bibliometric and citation analysis approaches [15].

Title and abstract screening of the 100 records was conducted independently by four reviewers based on predefined inclusion criteria (relevance to propofol induction, peer-reviewed articles, and English-language publications). Disagreements were resolved through discussion, and a fifth reviewer was consulted when necessary.

Figure 1. PRISMA flow diagram of included and excluded records.

Following screening, 40 studies were excluded based on eligibility criteria. The remaining eligible studies were further assessed, and the 50 most-cited articles were included in the final bibliometric analysis.

A PRISMA 2020 compliant flow diagram was used to report the study selection process, including identification, screening, eligibility, and inclusion stages, to ensure transparency and reproducibility [16].

Data extraction

Data extraction was performed independently by four reviewers using a standardised data extraction form adapted and modified from established bibliometric methodology [15]. Extracted variables included total citations, annual citation rates, journal impact factors, first author, year of publication, study design, level of evidence, and country or region of origin, consistent with established bibliometric indicators commonly reported in performance analysis studies [15]. Any discrepancies were resolved through discussion until consensus was reached among the reviewers.

Statistical analysis and visualisation

Statistical analyses were performed using IBM SPSS Statistics for Windows, Version 30.0 (IBM Corp., Armonk, NY, USA).

Descriptive statistics were used to summarise study characteristics. Continuous variables were reported as mean, median, and range, while categorical variables were presented as frequencies and percentages. Citation patterns and temporal trends were analysed and visualised to describe the evolution of research in propofol induction [16].

Results

Bibliometric overview of the top-cited propofol induction literature

As shown in Table 1, citation counts demonstrated a highly skewed distribution, with values ranging from 217 to 58 citations. A clear separation was observed between the top-ranked studies (Ranks 1-10 = 217-138 citations) and the remaining articles (Ranks 11-50 = 135-58 citations), indicating the presence of a small number of highly influential publications.

Table 1. Top 50 most-cited studies on propofol induction: title, first author, year of publication, and total citation count.

Overall, the dataset demonstrated a total of 5,252 citations, with a mean of 105.0 citations per article and a median of 92. The h-index of the dataset was 50, reflecting both a strong concentration of highly cited “landmark” studies and a sustained mid-range citation impact across the included literature.

These findings suggest that propofol induction research is driven by a limited number of highly influential studies, alongside a broader body of moderately cited work contributing to clinical and methodological advancements.

Temporal distribution of the top-cited propofol induction studies

Figure 2 shows a relatively balanced distribution across decades, with equal representation in the 2000-2009 and 2010-2020 periods (n = 18; 36.0% each). This reflects sustained interest in refining propofol induction protocols during an era of advances in pharmacokinetic modelling, safety optimisation, and international collaboration.

The late 1990s accounted for 14 articles (28.0%), representing the formative stage in which propofol’s clinical advantages were established across different surgical contexts.

Although the 2020s are not represented in this dataset, the distribution suggests that high-impact contributions emerged steadily over time rather than in a single innovation surge, indicating a continuous accumulation of practice-defining evidence over more than two decades.

Journal distribution of the top-cited propofol induction articles

Table 2 shows that nine journals are represented, indicating a strong concentration within a limited number of anaesthesia-focused outlets. The British Journal of Anaesthesia dominates the field, publishing 26 articles (52%) and accounting for the highest citation output, reflecting its central role in high-impact anaesthesia pharmacology research.

The next most frequent journals were Anaesthesia (n = 7) and Acta Anaesthesiologica Scandinavica (n = 6), followed by the European Journal of Anaesthesiology (n = 4).

Two journals, PLoS One (n = 2) and Paediatric Anaesthesia (n = 2), contributed more than one publication each. The remaining journals (BMC Anesthesiology, Current Opinion in Anesthesiology, and International Journal of Obstetric Anesthesia) each contributed a single article.

Overall, the findings demonstrate a clear concentration of influential propofol induction research within a small group of high-impact anaesthesia journals.

Figure 2. Decade-wise distribution of the top 50 most-cited propofol induction studies.

Table 2. Distribution of included studies by journal, total citations, and impact factor.

Geographic distribution of propofol induction research

As illustrated in Figure 3, the geographical analysis identified 50 country occurrences across the included studies, reflecting the extent of international collaboration. Each country appearing in a study’s author affiliations was counted once; therefore, multi-country studies contributed multiple country occurrences. This approach captures the breadth of cross-national participation in propofol induction research beyond the number of included studies alone.

The United Kingdom was the leading contributor (n = 17; 34%), followed by Germany (n = 7; 14%). South Korea, China, and Japan each contributed three publications (n = 3; 6%). Belgium and Singapore each contributed two publications (n = 2; 4%).

Additional single-country contributions (n = 1; 2%) were observed from Finland, the Netherlands, France, Italy, Switzerland, Sweden, Denmark, Canada, the United States, New Zealand, and Taiwan.

Overall, the results demonstrate a wide international distribution, with a notable contribution from both European and Asian countries.

Evidence levels (Oxford CEBM Framework)

As shown in Table 3, the evidence distribution follows the Oxford Centre for Evidence-Based Medicine (CEBM) framework. Level I evidence, including systematic reviews, meta-analyses, and high-quality randomized controlled trials, accounted for 28 studies (56.0%). Level II evidence (n = 12; 24.0%) consisted of randomized controlled trials and well-designed comparative studies with control groups. Level III evidence (n = 2; 4.0%) included non-randomized prospective cohort studies, while Level IV evidence (n = 7; 14.0%) comprised case series and retrospective studies. Level V evidence (n = 1; 2.0%) included expert opinion and narrative reviews.

Study design profile

As presented in Figure 4, the study design profile shows that RCTs (n = 23; 46.0%) represent the most frequent study type among the top-cited literature. These are followed by prospective, non-randomized cohort, or observational studies (n = 17; 34.0%), and case series or retrospective studies (n = 4; 8.0%). Systematic reviews and meta-analyses (n = 4; 8.0%) are also present in the dataset. The remaining studies consist of expert opinion or guideline papers (n = 2; 4.0%).

Figure 3. Geographic distribution showing the top contributing countries.

Table 3. Level of evidence distribution according to Oxford CEBM categories of the top-cited propofol induction articles.

Figure 4. Study design profile of the top-cited articles.

Discussion

This bibliometric analysis of the top 50 cited articles on propofol use in anaesthesia induction highlights efficacy, safety, and innovations. To our knowledge, this is among the first bibliometric analyses examining propofol use in anaesthesia induction. It measures the influence of citations and the progression of the evidence, thereby validating its fundamental importance in contemporary anaesthesia. Propofol remains central to modern anaesthesia due to its favorable pharmacokinetic profile and versatility in induction and maintenance [17,18]. Our findings show that a cluster of highly cited pillar studies, notably RCTs focusing on dosage accuracy, comparative efficacy, and safety optimisation, significantly impact the field. For example, [19] established that propofol has antiemetic properties, and [20] examined opioid interactions during induction; however, a notable gap exists in Level I evidence. Despite the abundance of RCT data (46%), systematic reviews comprise only 8% of the literature, which impedes evidence-based standardization of propofol protocols. The right-skewed distribution of the citation curve (range: 217-58) reflects a heavy-tailed distribution, where the top 10% of articles garner 40% of total citations, a pattern that indicates a field dominated by a few landmark studies. After the top 10 papers, which have totals between 217 and 138, there is an apparent decline in citations. This pattern draws attention to key investigations that greatly affect debates on propofol induction’s efficacy, dosage approaches, and induction process safety. The overall impact is substantial with 5,252 total citations, an average of 104.1 citations per article, a median of 91, and an h-index of 50. This demonstrates a mature field in which core pillars coexist with growing research to improve practice constantly. Seminal articles on pharmacokinetic–pharmacodynamic modelling [18] indicate the field’s transition to evidence-based practice. The temporal distribution of articles throughout three discrete eras suggests continual refining rather than discontinuous change. The late 1990s studies, such as [19]’s work on Postoperative nausea and vomiting and [21]’s meta-analysis on the same topic, established criteria for assessing induction, efficacy, and safety. In the 2000s, this line of research gained traction through comparative trials, such as [20] investigation of opioid combinations with propofol for loss of consciousness. From 2010 to 2020, research increasingly focused on pharmacokinetic accuracy. The comprehensive pharmacokinetic-pharmacodynamic model developed by [18] received the highest citation count (217). The emphasis on pharmacokinetics from 2010 to 2020 coincides with the rise of precision anaesthetic approaches, drawing on early work in the late 1990s that established EEG monitoring as a cornerstone for measuring anaesthetic depth [22,23]. This time frame corresponds to the typical pharmaceutical research lifecycle, which includes first efficacy demonstrations, comparative effectiveness studies, and safety refinement. The observed geographic concentration is particularly notable, with 66% of publications originating from Europe. This geographic bias may limit the generalizability of dosing recommendations across diverse patient populations with varying genetic pharmacokinetic profiles, body compositions, and comorbidity patterns common in different regions. The underrepresentation of research from developing countries, where resource constraints may necessitate different anesthetic approaches, suggests potential gaps in evidence applicable to global clinical practice. This concentration raises fundamental questions about the global applicability of study findings, especially given the wide variation in anesthetic practice, patient populations, and healthcare systems among countries [23]. Generalisability is further restricted by the absence or underrepresentation of several world regions. South Korea has been noted as an emerging country contributing to research [24]. There is a significant number of publications in a few journals, with the BJA accounting for 26 of the 50 articles and receiving 2,914 citations. Beyond geographic disparities, examining methodological trends within the literature provides further insights into articles and publication patterns. Methodological quality is a critical determinant of the strength of scientific evidence. RCTs have played a fundamental role in developing evidence-based treatment guidelines, for example, determining appropriate doses for specific groups such as children [25]. However, very few studies were systematic reviews or meta-analyses (8%). This indicates a lack of studies that pool and summarize evidence. Although such studies would support more robust clinical decision-making and evidence-based guideline development [19], it was also noted that most of the evidence is based on Level I and Level II research (56% and 24%, respectively). However, 18% of the evidence comes from levels III and IV, such as observational studies or case reports. Despite the significant development in clinical trial design, observational studies remain very important, especially in cases where it is difficult or unethical to conduct randomised trials, such as critically ill patients or rare conditions [26]. This bibliometric study has several limitations, the most important of which are citation bias, geographic and methodological bias, and limitations in the scope of the analysis. Generalizing the results is difficult, as most studies were published in European countries, making it difficult to assess genetic variation. The results of the study may be influenced by geographic and methodological bias. Furthermore, the dominance of the British Journal of Anaesthesia further amplified this geographic bias. It skews the results to reflect European practitioners’ and researchers’ priorities and methodologies, ignoring valuable research published in other journals. The study also focused on the number of citations and did not analyse citation patterns, which may not fully reflect current research priorities or clinical relevance. The study did not include studies after 2020, which excluded recent developments in anaesthesia practice, such as changes related to the COVID-19 pandemic and new medical monitoring technologies. Lastly, the analysis reveals a lack of systematic reviews (8%), which may be unpublished or not indexed in the databases used. Observational studies, like [26], received fewer citations, possibly due to practical constraints rather than methodological preferences. Despite these limitations, the analysis sheds light on the foundational research that has shaped modern propofol induction practice, emphasizing the impact of pivotal studies on current protocols for vulnerable populations such as pediatric patients and pregnant women [25,27]. Bibliometric research on anaesthesia, such as that of [28], has yielded comparable results. Their findings are consistent with our investigation, which found that propofol-related literature predominantly centres on safety, pharmacokinetics, and sedation, with citations dominated by a few major publications. Their analysis echoes this, highlighting a similar thematic concentration and citation pattern of pharmacokinetics and sedation, with citations dominated by a few central articles and a diverse focus. These comparisons show that the gaps and clusters identified in this investigation are not isolated. Rather, these patterns reflect a broader trend in the anaesthesia literature, underscoring the importance of diversifying research sources and pooling evidence. Furthermore, our findings on the established role of propofol are corroborated by recent clinical evidence. For instance, a systematic review and meta-analysis by [29] confirmed that propofol remains a safe and effective standard for general anaesthesia induction and maintenance. While their study reveals that newer drugs, such as ciprofol, may improve specific recovery dynamics, it ultimately validates propofol’s core and foundational position in modern anaesthesia practice, which is consistent with the influential status indicated by our bibliometric analysis.

Recommendations

Based on the findings of this bibliometric analysis, several directions for future research are proposed.

Future studies should prioritise large-scale, multinational collaborations, particularly involving underrepresented regions. This would enhance the external validity and global relevance of the evidence base in propofol research.

There is a need for a greater focus on high-quality systematic reviews and meta-analyses to better consolidate the existing body of clinical evidence derived from primary studies, particularly RCTs.

Future research should aim to strengthen the integration between primary clinical investigations and higher level evidence synthesis to improve the coherence and clinical applicability of propofol-related literature.

Conclusion

This bibliometric analysis provides a quantitative overview of the intellectual structure and temporal evolution of research on propofol induction over the past three decades. The findings indicate that propofol remains a cornerstone agent in anaesthetic practice, with a strong concentration of highly cited literature originating from European institutions and journals. RCTs represent the predominant study design among the most influential publications.

In addition, the analysis highlights a relative underrepresentation of evidence synthesis studies, such as systematic reviews and meta-analyses, within the most highly cited literature. The observed geographic concentration of research output may also have implications for the broader applicability of the available evidence across different populations and healthcare settings.

In summary, while the clinical effectiveness of propofol is well established, future progress in this field will depend on improving geographic diversity and strengthening evidence synthesis to support more comprehensive and globally applicable anaesthetic practice.

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