Rapid aging of the global population has led to an increased need for large-scale surgical and peri-surgical care for older people.[1] In 2030, there will be about one in six people in the world over 60 years old, most of whom will reside in low- and middle-income countries.[2] This age shift is of significance to surgical services, as more elderly patients are having more complex surgeries that demand personalized anesthetic care.[3]

Physiological changes in cardiovascular, respiratory, renal, hepatic, and neurological function are associated with advanced age; additionally, high rates of multimorbidity, frailty, and polypharmacy (multiple medications) and low physiological reserve are associated with advanced age.[4] Older patients are therefore at greater risk of hemodynamic instability, delayed clearance of drugs, postoperative respiratory complications, delirium, pain, nausea and vomiting, prolonged hospital stay, and other complications

after anesthesia and major surgery.[5] A large study involving surgical patients revealed that older age was associated with increased postoperative morbidity and mortality rates. [6, 7] The results highlight that chronological age is not enough to define the perioperative risks and that anesthetic planning must take into account the biological and clinical variability of older patients.

Biological sex and gender are other factors that are less studied regarding anesthetic response.[8] Studies have suggested that women and men may have different concentrations, distribution, metabolism, and elimination of some drugs, and women have been observed to have elevated drug levels and longer elimination half-life for many drugs given at similar doses.[9, 10] In the field of anaesthesia, recent research has indicated sex-based distinctions in the reactions to widely-used agents such as propofol, opioids and neuromuscular blocking drugs, and in the postoperative pain experience, recovery and complication rates.[11] Importantly, sex and gender are different concepts: sex can affect pharmacological and physiological responses, and gender can affect health behaviors, communication, expectations, access to care and interactions with health systems. These can therefore also be associated with differences in peri- and postoperative outcomes.[12]

However, traditional anesthetic practice often uses a one-size-fits-all approach to dosing and other perioperative management techniques, without accounting for the unique physiology or pharmacology of males and females.[13] In older adults, age-related pharmacokinetic changes are overlaid on sex-related differences and physiological changes, making this method especially applicable to this population. It is therefore possible that a one-size-fits-all approach to anaesthesia will not be able to account for clinically relevant differences in anaesthetic requirements, haematodynamics, analgesic requirements, emergence from anaesthesia, and postoperative morbidity.[14]

Personalized medicine is an emerging theme in modern perioperative medicine, but the incorporation of sex-specific factors into anesthetic selection for older patients who need major surgery has not been fully examined.[15]

In this context, gender-specific anesthesia is a possible next step in precision medicine during perioperative care, which transcends the belief that the same anesthesia plan is suitable for all older patients. Awareness of sex and gender differences can enable anesthesiologists to more precisely adjust drug selection and dosage, predict differential adverse events, optimize analgesia, and customize postoperative monitoring based on an individual's risk. This could be especially useful in resource-limited health systems where one might expect to see significant benefits in recovery post-surgery and avoid unnecessary healthcare utilization if complications during surgery are avoided. Hence, the present study was carried out to compare anaesthetic practice and outcome parameters between the genders of older patients undergoing major surgery, especially in relation to anaesthetic requirement, hemodynamic stability, postoperative complications, recovery profile and surgical outcome.

A prospective comparative observational study was conducted in the Department of Anesthesia. The study was conducted over a period of six months, from July to December, 2025. Sample size for comparison of two independent means was determined using OpenEpi version 3.01. The calculation was done on the basis of results of Bajaj et al., who had assessed emergence from general anaesthesia in 120 cases comprising 60 male and 60 female patients. In that study, the mean time from discontinuation of anesthesia to eye opening was 6.87 ± 2.54 minutes for women and 8.78 ± 2.66 minutes for men, which is a statistically significant difference (P < 0.001). Based on these values, a two-sided 95% confidence level, 80% statistical power, and an allocation ratio of 1:1, a minimum sample size of 60 patients (30 in each group) was calculated. A sample size of 68 patients was used to offset about 10% potential lost samples or lack of postoperative follow-up. The final number of samples was thus rounded off to 70 patients, representing 35 males and 35 females. A non-probability consecutive sampling technique was used. Patients included were adults 65 years or older, both sexes, and were planning elective major surgical procedures under general anesthesia. Included were patients with American Society of Anesthesiologists (ASA) physical status I–III.[16] Patients had to give informed consent to enter and follow up on the study. Major surgical procedures included those likely to require general anesthesia and extensive perioperative monitoring, which were defined as procedures involving the major organs and systems of the body, such as the abdominal organs, thoracic organs, orthopedic, urologic, gynecologic, and other comparable surgeries. Patients who were treated with emergency surgery, regional or neuraxial anesthesia as the main anesthetic technique, or a combined anesthetic technique that prevented estimating general anesthetic requirements and emergence were excluded. Also, patients with severe neurological or cognitive impairment before their surgery were not included. Other exclusions were severe liver or kidney failure (dialysis or advanced organ support therapy), known allergy or contraindication to the anesthetic agents used during the trial, preoperative mechanical ventilation, and inability to give informed consent, or inability to complete postoperative assessment. Patients who failed to have any anesthesia record or incomplete perioperative outcome data were also excluded from the final analysis. All participants gave informed consent before their participation. Demographic and clinical data were collected, such as age, sex, body mass index, ASA physical status, pertinent medical comorbidities, smoking history, preoperative hemoglobin, and type and duration of surgery. A standardized anesthetic protocol was followed as clinically appropriate for all participants. Anesthetic depth was monitored by routine electrocardiography and non-invasive or invasive blood pressure monitoring as necessary for the patient, pulse oximetry, end-tidal carbon dioxide, respiratory rate, and continuous assessment of anesthetic depth if available. Records of doses of induction agents, opioids, inhalational and intravenous maintenance anesthetics, muscle relaxants, and reversal agents were made. Anesthetic drug requirements were estimated based on patients' true body weight and clinically relevant adjustment of anesthetic doses. The intra-operative hemodynamic parameters such as hypotension, hypertension, bradycardia and tachycardia were documented along with the need for vasopressor or other cardiovascular support. Emergence and recovery were systematically evaluated after the surgery. Time to spontaneous eye opening, response to verbal commands, and extubation of the endotracheal tube were noted. Intensity of pain, need for rescue analgesics, development of postoperative nausea and vomiting, respiratory complications, hemodynamic instability, delayed emergence, postoperative delirium, and admission to the intensive care unit were reported. The length of stay in the post-anesthesia care unit and total hospital stay after the anesthesia were also documented. Patients were followed up in the immediate post-operative period to look for early complications and outcomes of treatments. The main outcome was the time to emerge from general anaesthesia, measured primarily by the time to eye opening and response to verbal command, between male and female older patients. Secondary outcomes were total anesthetic dose, intraoperative hemodynamic stability, requirement for vasopressors, postoperative pain, postoperative nausea and vomiting, respiratory complications, delayed emergence, postoperative delirium, PACU stay, and length of hospital stay. Data were coded and analyzed using SPSS (version 26.0) software on IBM PCs. The Shapiro–Wilk test was used as an initial measure to test for normality in continuous variables. Continuous data with normal distribution were given as mean ± standard deviation, and continuous data with non-normal distribution were given as median (interquartile range). Frequencies and percentages were used to describe categorical variables. Normally distributed continuous variables were compared between the two groups (Male vs Female patients) using an independent-samples t-test, and non-normally distributed continuous variables were compared between the two groups using the Mann–Whitney U test. The chi-square test and Fisher's exact test were used to compare categorical variables. The two sex groups were compared for differences in anesthetic drug requirements, emergence times, and hemodynamic events during the anesthetic, postoperative complications, and recovery parameters. Multivariable regression analysis was used if patient sex remained a significant covariate after controlling for other potential confounding factors to determine if sex was independently associated with important perioperative outcomes. Clinically relevant and/or statistically significant variables in the univariable model were included in the multivariable model. Potential confounding factors were age, BMI, ASA status, time of surgery, surgery type, and major comorbidities. Confidence intervals were reported for the effect. A p-value of <0.05 was considered statistically significant. significant.

A total of 70 older patients were included, comprising 35 males and 35 females. The demographic and clinical characteristics of the two groups were generally similar in terms of age, BMI, ASA physical status, and primary comorbidities. Smoking was, however, significantly more frequent in males, and females had significantly lower preoperative hemoglobin levels. The distribution and duration of the major surgical procedures were similar between the groups and so were likely to have little role in the differences observed in anesthetic outcomes (Table 1).

There were markedly higher requirements for a number of anesthetic agents in men. The median doses of propofol, fentanyl, and rocuronium were higher for males than females, while there were no significant differences in sevoflurane exposure, use of reversal agents, or extra opioid requirements. The average time of surgery was also comparable in both groups (Table 2).

Intraoperative hemodynamic parameters such as mean arterial pressure and frequencies of hypertension, bradycardia, tachycardia, and arrhythmia were similar. However, males experienced a significantly greater number of hypotensive episodes and required higher doses of norepinephrine. Males were more likely than females to be using a vasopressor, but the difference between the groups was not statistically significant (Table 3).

Actually, differences in emergence and post-operative analgesic needs were found. Females were able to achieve eye opening, response to verbal commands, and extubation significantly earlier than males. In contrast, females had higher pain scores in the early post-operative period, and demanded more morphine-equivalent pain relief. The duration of PACU and hospital stays were similar between groups (Table 4).

The differences in the incidence of postoperative nausea and vomiting, respiratory complications, hypoxemia, and delirium were not significant between the genders. There were similar rates of overall postoperative complications, ICU admission, 30-day readmission, and 30-day mortality between groups (Table 5).

Multivariate analysis showed that being male was independently associated with longer time to eye opening after adjusting for age, BMI, ASA status, surgery time, propofol dose, and major comorbidity. The following factors were also independently associated with prolonged emergence: increasing age, ASA III status, longer surgery, and higher propofol exposure. In contrast, postoperative complications were independently associated with surgery lasting ≥120 minutes and intraoperative hypotension, while sex itself was not an independent predictor of postoperative complications (Table 6).

Table 1. Demographic and clinical characteristics of study participants

Table 2. Surgical characteristics and intraoperative anesthetic requirements

Table 3. Intraoperative hemodynamic outcomes

Table 4. Emergence, postoperative pain and recovery outcomes

Table 5. Postoperative complications and clinical outcomes

Table 6. Multivariable regression analysis of factors associated with perioperative outcomes

1. Linear regression for time to eye opening

1. Logistic regression for postoperative complications

In the present study, clinically relevant sex differences were identified in the postoperative recovery and anesthetic needs of older patients undergoing major surgery. Patients had significantly more propofol, fentanyl, and rocuronium administered to them, and women had significantly quicker emergence from general anesthesia. Median time to eye opening was 8.2 minutes in men and 6.4 minutes in women, while women were quicker to respond to verbal command and extubate the trachea. Moreover, women reported a higher degree of postoperative pain and needed more pain medication in the postoperative period, in terms of morphine-equivalent doses. Postoperative nausea and vomiting (POVN) and overall postoperative complications were numerically more common among women, but were not statistically significantly different. Importantly, age, BMI, ASA status, surgical duration, propofol dose, and comorbidity were found to be associated with longer time to eye opening in bivariable analysis; in multivariable analysis, the association with male sex was independent. The patients' appearance from the anesthesia was observed in women, as done by Braithwaite et al. (2023) in a systematic review and meta-analysis of 64 studies and 98,243 patients. Their analysis showed that females emerged earlier than males, with differences of −2.28 and −2.84 minutes for eye opening and for responding to the verbal command, respectively. The odds for awareness were also higher for women in the postoperative recall group. The finding of a shorter time to eye opening (1.8 minutes by us) and shorter time to response to verbal command (approx. 2 minutes by us) among women supported the contemporary evidence. Our difference was slightly smaller than the pooled estimates, which may be due in part to the older age of our subjects and the fact that multiple anesthetic agents were used, not necessarily a strictly controlled protocol of propofol alone.[17] More recently, Rahe et al. (2025) analysed propofol/remifentanil anaesthesia in 876 patients, and focused particularly on the impact of age and sex on propofol consumption and emergence. Their multivariable analysis showed age and sex to be significant factors, and that there was a significant age-sex interaction in terms of propofol requirement. This observation strengthens our results that anesthetic requirements are not necessarily independent of age and sex. Median doses of propofol were higher in men compared to women in our cohort, and older age had a significant independent effect on emergence duration. The agreement between these results is especially relevant since anesthetic pharmacokinetics and pharmacodynamics variables may be increased with advancing age, exacerbating real clinically relevant differences between the two sexes.[18] The current results also confirmed the general evidence presented by Filipescu et al. (2021), which highlighted how biological sex can affect anesthetic pharmacokinetics, pharmacodynamics, pain management, post-anesthetic recovery, adverse effects and perioperative safety. Instead, they insisted that sex must be taken into account in the pre-op assessment in addition to the normal risk factors and not just as a demographic factor. This is reinforced by our finding that, after adjusting for several clinical confounders, male sex was an independent risk factor for a longer emergence duration.[19] The present results must, however, not be interpreted as that there is a difference in dosage between the sexes, but that sex may be another parameter used in individual dosing, along with other parameters such as age, organ function, body composition, comorbidity, and anesthetic depth. Our results of higher postoperative pain in females were similar to those of Kanaan et al. (2021), who compared 585 patients who received lumbar spine surgery and identified a significant increase in postoperative pain in females after adjusting for covariates. The authors noted that the difference was not clinically significant, but the results showed that there may still be differences in postoperative pain between genders after controlling for other clinical variables. In our study, pain was significantly higher, and median scores were higher at 1 h and 6 h after surgery in women, which also more morphine-equivalent dose in the postoperative period.[20] Despite this similarity between the two studies, there is evidence that sex differences in post-operative drug requirements may still exist in older surgical patients, albeit the size of these differences may differ depending on surgical procedure and pre-operative pain levels. This greater amount of analgesia also matched the results of Andreoletti et al. (2022), who performed a systematic review and meta-analysis of age, sex and preoperative pain as risk factors for chronic postsurgical pain. They also noted that sex was one of the patient-level factors that was associated with postoperative pain outcomes and that age and preoperative pain were important potential confounders.[21] The nature of this applies especially to our population since all were older adults, and age-related changes in pain sensitivity, drug sensitivity, and physiological reserve were pertinent. In the present study, the increased postoperative opioid use in women should not be regarded as a purely biological sex effect, as many other factors could explain this difference, such as preoperative pain, procedure type, comorbidities, and psychosocial factors. In the present study, the relationship of sex with wider postoperative complications seemed to be more complex. Women had a higher number of postoperative complications than men (48.6% vs 37.1%), but this was not a significant association in multivariable analysis. Surgery of ≥120 minutes, however, and intraoperative hypotension were independently associated with postoperative complications. This is a significant finding as it implies that if there are differences in anesthetic response between sexes, then this does not directly correspond to differences in major postoperative morbidity. In a large, two-centre retrospective cohort study of the association between anesthesia-provider sex and perioperative complications, von Wedel et al. (2024) also reported an emphasis on factors other than sex. Their findings showed that sex alone is not the sole determinant of their work perioperative outcomes; rather, they found a number of factors that interact to influence their work outcome. The researchers said that while their exposure was the type of anesthesia given to the patient rather than the type given by the provider, the results underscore the need to refrain from making simple causal attributions for sex-related differences in outcomes.[22] The main advantage of the present study was that it evaluated anesthetic requirement, emergence, hemodynamic stability, postoperative pain, complications, and recovery till discharge in a pure population of elderly surgical patients. This association between male sex and delayed emergence was also confirmed using multivariable regression, which was adjusted for a number of important clinical variables. However, the study was limited in generalizability by the relatively small sample size and the single-center study design, observational study design and differences in surgical procedures. Furthermore, sex-related differences may not have been fully distinguished from differences in body composition, comorbidity, hormone levels, preoperative pain, and psychosocial factors. The study also looked at sex as reported in the clinical record, not at all at the level of comprehensively assessing gender-related factors. Further prospective multicenter studies with pharmacokinetic assessments, depth of anesthesia, frailty status, cognition, and hormone status and with patient-reported outcomes are warranted. In general, the present results indicated that older men and women were not equally affected by general anesthesia. Men needed more dosages of some of the anesthetic agents and were slower to emerge from anesthesia; women had higher levels of pain and higher opioid requirements after anesthesia. However, no single factor, alone, was found to be a strong independent predictor of major postoperative morbidity, as surgical duration and intraoperative hypotension were more important. These findings suggest a new approach in older adults, moving towards a more personalized anesthetic approach where sex-specific differences are acknowledged but combined with age, frailty, comorbidities, surgical complexity and physiological response. Limitations There were some limitations in this study. First, the relatively small number of 70 patients restricted the power to recognize differences in less common outcomes like postoperative delirium, admission to an intensive care unit, hospitalization, or mortality. Secondly, the study was done at a single tertiary care hospital, which might have restricted the results to other hospitals and patient groups. Third, the observational design precluded the possibility of drawing causal inferences between exposure to anesthetics of different sexes and perioperative outcomes. This may also have caused heterogeneity in anesthetic needs and recovery in the different types of major surgical procedures performed. Although important confounding factors were adjusted for in multivariable analysis, residual confounding related to frailty, preoperative pain, body composition, hormonal status, cognitive function, and socioeconomic factors could not be completely excluded. Lastly, the study was restricted to biological sex and failed to thoroughly evaluate gender-related factors that could be associated with communication, pain perception, health care seeking, and recovery.

There was a difference in anesthetic requirements and recovery after surgery in elderly patients between males and females after their major surgeries. Women were more likely to experience more postoperative pain and opioid analgesia, and men were more likely to have higher doses of multiple anesthetic agents and slower emergence. Clinical and surgical factors, however, accounted for the difference in overall postoperative complications, with sex not making a difference. These results support an individual anesthetic strategy that takes into account age, comorbidities, surgical complexity, and depth of anesthetic and physiological response as well as sex. Future larger multicenter prospective trials are required to determine the benefit of sex-specific anesthetic strategies on clinically relevant postoperative outcomes.

1. Gencer, B., et al., European Society of Cardiology quality indicators for the cardiovascular pre-operative assessment and management of patients considered for non-cardiac surgery. Developed in collaboration with the European Society of Anaesthesiology and Intensive Care. European Heart Journal-Quality of Care and Clinical Outcomes, 2023. 9(4): p. 331-341.
2. Mathews, C., Population ageing in lower-and middle-income countries. Celebrating 40 years of HelpAge International. Journal of Population Ageing, 2024. 17(1): p. 1-4.
3. Luca, E., et al., Implication of age-related changes on anesthesia management. Saudi Journal of Anaesthesia, 2023. 17(4): p. 474.
4. Alsararatee, H.H., How do physiological ageing and frailty affect human body systems? Journal of Prescribing Practice, 2025. 7(9): p. 382-389.
5. Van Zundert, T.C., S.P. Gatt, and A.A. van Zundert, Anesthesia and perioperative pain relief in the frail elderly patient. Saudi Journal of Anaesthesia, 2023. 17(4): p. 566.
6. Endeshaw, A.S., et al., Perioperative outcomes among older surgical patients with multimorbidity: a longitudinal study from Ethiopia. BMC public health, 2025. 25(1): p. 2641.
7. Zegeye, S.T., et al., Determinants of 28-day perioperative mortality and postoperative length of hospital stay among geriatric patients: a two-center prospective follow-up study in Ethiopia. BMC geriatrics, 2026. 26(1): p. 444.
8. Wasilczuk, A.Z., et al., Hormonal basis of sex differences in anesthetic sensitivity. Proceedings of the National Academy of Sciences, 2024. 121(3): p. e2312913120.
9. Aljohmani, A. and D. Yildiz, Biological sex differences in pharmacokinetics and adverse drug reactions. Naunyn-Schmiedeberg's archives of pharmacology, 2026. 399(3): p. 3285-3301.
10. Lee, S.-M., J.-H. Jang, and S.-H. Jeong, Exploring gender differences in pharmacokinetics of central nervous system related medicines based on a systematic review approach. Naunyn-Schmiedeberg's Archives of Pharmacology, 2024. 397(11): p. 8311-8347.
11. Gourier, S., et al., Sex-based differences in anesthesia approaches and outcomes: a narrative review. Anaesthesia Critical Care & Pain Medicine, 2025: p. 101723.
12. Becher, E. and S. Oertelt-Prigione, The impact of sex and gender in medicine and pharmacology, in Sex and gender effects in pharmacology. 2023, Springer. p. 3-23.
13. Mayet, S., Towards ethically grounded shared decision-making in anaesthesia: integrating principles and practice. 2024, Stellenbosch: Stellenbosch University.
14. Stader, F. and C. Marzolini, Sex-related pharmacokinetic differences with aging. European geriatric medicine, 2022. 13(3): p. 559-565.
15. DiMaria, S., et al., Genetic variation and sex-based differences: current considerations for anesthetic management. Current issues in molecular biology, 2025. 47(3): p. 202.
16. Porcaro, A.B., et al., American Society of Anesthesiologists (ASA) physical status system predicts the risk of postoperative Clavien–Dindo complications greater than one at 90 days after robot-assisted radical prostatectomy: final results of a tertiary referral center. Journal of Robotic Surgery, 2023. 17(3): p. 987-993.
17. Braithwaite, H.E., et al., Impact of female sex on anaesthetic awareness, depth, and emergence: a systematic review and meta-analysis. Br J Anaesth, 2023. 131(3): p. 510-522.
18. Rahe, C. and B. Schultz, Age- and sex-specific differences in propofol consumption and extubation time: An analysis of a data set from an observational multicenter trial. Medicine (Baltimore), 2025. 104(16): p. e42176.
19. Filipescu, D. and M. Ştefan, Sex and gender differences in anesthesia: Relevant also for perioperative safety? Best Pract Res Clin Anaesthesiol, 2021. 35(1): p. 141-153.
20. Kanaan, S.F., et al., The effect of age and gender on acute postoperative pain and function following lumbar spine surgeries. Physiother Res Int, 2021. 26(2): p. e1888.
21. Andreoletti, H., et al., A systematic review and meta-analysis of three risk factors for chronic postsurgical pain: age, sex and preoperative pain. Minerva Anestesiol, 2022. 88(10): p. 827-841.
22. von Wedel, D., et al., Association of anaesthesia provider sex with perioperative complications: a two-centre retrospective cohort study. Br J Anaesth, 2024. 133(3): p. 628-636.