Abstract
Background
In neuroanesthesia, a prompt emergence from anesthesia is essential for postoperative neurologic assessment. Intraoperative infusion of sodium bicarbonate Ringer’s solution (BRS) and lactated Ringer’s solution (LRS) have different effects on internal environment, potentially contributing to discrepant recovery profiles. Therefore, this study aimed to compare the recovery of BRS and LRS in patients undergoing craniotomy for supratentorial tumors.
Methods
This randomized controlled trial enrolled patients undergoing elective supratentorial tumor resection. Patients were randomized to receive BRS or LRS for intraoperative fluid therapy. The primary outcome was emergence time. Secondary outcomes included extubation times, short Orientation Memory Concentration Test (SOMCT) at 15 min after extubation and postoperative complications. Parameters including lactic acid (Lac), pH, base excess (BE), and serum Mg2+ levels were measured at several time points and compared between the two groups. Total length of hospital stay was also recorded and compared between the two groups. Primary analysis followed the intention-to-treat (ITT) principle. A per-protocol (PP) sensitivity analysis was also performed for the primary outcome.
Results
The ITT analysis included 100 patients (BRS group: n = 50; LRS group: n = 50). Following exclusions for short surgery or massive intraoperative blood loss, the PP set included 48 BRS and 47 LRS patients. In the ITT analysis, Patients assigned to the BRS group had shorter emergence (13min vs 16min; median difference, 3; 95% CI, 1 to 4; P=0.003) and extubation times (15min vs 18min; median difference, 2; 95% CI, 1 to 4; P=0.01), and lower lactate levels at the end of surgery and 0.5 hour after extubation (P < 0.05). SOMCT scores at 15 min after extubation, postoperative complications and total hospitalization days were comparable between the groups (P > 0.05). Additionally, no significant group-by-time interactions were found for pH, BE and Mg2⁺ levels, indicating similar temporal changes between groups (P > 0.05).
Conclusion
Patients receiving BRS during supratentorial tumor resection had faster emergence and shorter extubation times, but similar SOMCT scores at 15 min after extubation and complication rates compared to those receiving LRS.
Trial Registration
Chinese Clinical Trial Registry, ChiCTR2500105691, registered on July 9, 2025.
Keywords: bicarbonate Ringer’s solution, lactate, emergence time, supratentorial tumor surgery
Introduction
Craniocerebral surgery is commonly associated with severe surgical trauma and intense systemic stress, which contributes to the high prevalence of postoperative delayed emergence from anesthesia.1 Delayed emergence increases the risk of pulmonary infection related to indwelling tracheal catheterization, and can mask the clinical manifestations of postoperative complications such as seizures, intracranial hypertension, and intracranial hemorrhage.2,3 In contrast, rapid recovery of consciousness facilitates timely neurological assessment and early intervention for postoperative complications.4 Accordingly, identifying effective interventions to promote rapid and complete recovery of postoperative consciousness has become a key research focus in intracranial surgery.
Growing evidence confirms that perioperative internal environment disturbance is an independent critical risk factor for delayed emergence in patients undergoing craniocerebral surgery.5 Intraoperative blood loss and surgical stress frequently induce acid-base imbalance and electrolyte disorders, which in turn inhibit central nervous system metabolism and delay the clearance of anesthetic drugs. Perioperative fluid therapy plays a pivotal role in maintaining internal environmental homeostasis, and rational selection of crystalloid solutions is essential for optimizing the quality of postoperative emergence.6–8
0.9% saline and lactated Ringer’s solution (LRS) are the primary crystalloids used for perioperative fluid management in patients undergoing intracranial tumor craniotomy, yet both have notable limitations during large-volume and prolonged intraoperative infusion. Excessive infusion of 0.9% saline is prone to inducing hyperchloremic metabolic acidosis,9 while the hypotonic property of LRS increases the risk of cerebral edema.6 Notably, brain tumor resection inherently triggers the accumulation of intraoperative cerebral extracellular lactate.10,11 Under this pathological condition, additional exogenous lactate intake from LRS infusion may further increase regional cerebral lactate burden, theoretically disturbing cerebral metabolic homeostasis and impairing postoperative anesthetic emergence. Additionally, studies have shown that large-volume infusion of LRS exacerbates intrinsic lactic acidosis and increases aerobic demand.12,13
Bicarbonate Ringer’s solution (BRS) is a novel lactate-free balanced crystalloid buffered with bicarbonate. Its electrolyte profile closely matches physiological levels, and it requires minimal hepatic and renal conversion. Recent studies have also shown that BRS has advantages in stabilizing the internal environment and shortening postoperative recovery time.14,15 Other reports suggest BRS may mitigate the accumulation of endogenous lactic acid.16 Accordingly, we hypothesized that the lactate-neutralizing capacity of BRS may optimize the cerebral microenvironment by regulating metabolically generated lactate. In addition, BRS contains 1 mmol/L magnesium, which has been proven to alleviate craniotomy-related cerebral vasospasm in prior studies.17
However, whether these comprehensive benefits of BRS facilitate earlier anesthetic emergence in patients undergoing supratentorial tumor resection remains unclear. On this basis, this study comparatively evaluated the clinical efficacy of BRS versus LRS in patients undergoing supratentorial craniotomy for tumor resection, and analyzed their effects on perioperative internal environmental parameters and emergence time.
Materials and Methods
This study was conducted at the 904th Hospital of the Joint Service Support Force of the Chinese People’s Liberation Army from July 2025 to July 2026, in accordance with the principles of the Declaration of Helsinki. Participants were divided into BRS group and LRS group, and all provided written informed consent. Ethical clearance was granted by the 904th Hospital of the Joint Service Support Force of the Chinese People’s Liberation Army on June 3, 2025 (NO.20250603), and it was registered at the China Clinical Trial Center before the first patient was enrolled (ChiCTR2500105691).
Participants
One hundred patients who underwent supratentorial tumor resection under general anesthesia were enrolled, with age 18–65 and American Society of Anesthesiologists (ASA) physical status I–III. Exclusion criteria included a preoperative Glasgow Coma Scale<15, a body mass index (BMI) >30 kg/m2, a history of craniotomy tumor resection, severe cardiopulmonary diseases, liver or renal dysfunction, a history of drug or alcohol abuse, allergies to any anesthetic, scheduled for electrophysiological monitoring and refusal for participation. The withdrawal criteria were short (<3h) or long (>6h) surgery duration, severe hemodynamic disturbances or other unexpected serious complications during the surgery, intraoperative blood loss exceeding 20% of total blood volume, or postoperative admission to ICU for continued mechanical ventilation.
Randomization and Blinding
The generated random allocation sequences (1:1 allocation ratio, with block sizes of 2 and 4) were placed in sequentially numbered opaque envelopes and sealed prior to the initiation of surgery. Before anesthesia induction, an independent researcher blinded to the randomization scheme opened the sealed envelopes, allocated patients to either the lactated Ringer’s group (LRS group) or the bicarbonate Ringer’s group (BRS group), and dispensed the corresponding intravenous fluids. Anesthesiologists were not blinded to the arm assignment due to the different packaging of investigated fluids. Since all patients were switched to normal saline before transfer to the post-anesthesia care unit (PACU) and extubation was performed in the PACU, the investigators assessing recovery and performing extubation were blinded to group allocation. In addition, participants, clinicians other than the attending anesthesiologist, data collectors and statisticians were kept blinded.
Anesthesia Management
After admission to the operating room, routine monitoring of electrocardiography, pulse oximetry, non-invasive blood pressure and bispectral index (BIS) was implemented. Invasive radial artery puncture and catheterization were performed under local anesthesia to continuously monitor invasive arterial pressure, arterial blood gas, cardiac output (CO), stroke volume variation (SVV). The induction of anesthesia was performed by sufentanil (0.3 μg/kg), propofol (2.0 mg/kg) and rocuronium (0.6 mg/kg). Tracheal intubation was performed once adequate muscle relaxation was achieved. Tidal volume was adjusted to 6–8 mL/kg to maintain the end - tidal carbon dioxide (EtCO2) concentration within the range of 35–45 mmHg. The maintenance of anesthesia involved propofol (2–4 mg/kg/h), sevoflurane (1%), rocuronium (5 ug/kg/min), remifentanil (0.1–0.3 μg/kg/min), and BIS 40–60. Sufentanil bolus (0.1ug/kg) was added before scalp incision and dural closure. Dexamethasone (5 mg) and ondansetron (5mg) were administered before the start of the surgery to prevent postoperative nausea and vomiting (PONV). Mannitol (20%,1g/kg) was infused within 20 minutes after scalp incision for satisfactory brain relaxation.
Patients in the Group LRS were intraoperatively infused with LRS, and those in Group BRS received BRS. LRS contains 130 mmol/L Na⁺, 4 mmol/L K⁺, 1.5 mmol/L Ca2⁺, 109 mmol/L Cl− and 28 mmol/L lactate with a pH of 6.5 and osmolarity of 273 mOsm/L, while BRS consists of 130 mmol/L Na⁺, 4 mmol/L K⁺,1.5 mmol/L Ca2⁺, 1 mmol/L Mg2⁺, 109 mmol/L Cl− and 28 mmol/L bicarbonate, with a pH of 7.3 and osmolarity of 276 mOsm/L. Fluids management is based on individualized goal-directed fluid therapy (GDFT): mean arterial pressure (MAP) maintained at 65–80 mmHg, SVV <13%.18 A baseline maintenance fluid of 2 mL/kg/h was given in all patients in both the groups. When SVV exceeded 13%, a 250mL crystalloid bolus was administered to correct relative hypovolemia. If SVV showed a decreasing trend even after fluid bolus, a second bolus of colloid was given and reassessed again at every 10 min. A fluid bolus was also administered as initial treatment in cases of hypotension (MAP < 65 mmHg). If no reduction was observed in SVV, fluid infusion was restricted and phenylephrine were given as appropriate to maintain stable cerebral perfusion pressure. Intraoperatively, episodes of hypotension, bradycardia (heart rate≤50 bpm), hypertension (MAP > 20% of baseline), tachycardia (heart rate≥100 bpm) were also noted.
For both groups, the rocuronium infusion and sevoflurane were discontinued at the end of dural closure, with fresh gas flow unchanged. Propofol and remifentanil infusions were stopped upon completion of the final skin suture, and this time point was recorded as the time of anesthetic discontinuation. The BIS target was maintained between 50 and 70 throughout this period. Following surgery, patients received normal saline as the maintenance fluid and were transferred to PACU for further observation. Sugammadex was routinely administered for neuromuscular blockade reversal in the PACU.
Outcomes
The primary outcome was emergence time, defined as the time from anesthetic discontinuation to eye opening, either spontaneous or in response to verbal stimulation. Patients were continuously observed for spontaneous eye opening. Verbal stimulation was performed every 2 minutes when no spontaneous eye opening occurred.
Secondary outcomes included tracheal extubation time, Short Orientation Memory Concentration Test (SOMCT) at 15 min after extubation and recovery complications. Tracheal extubation time was defined as the time from anesthetic discontinuation to tracheal extubation. Extubation was performed only when patients met the following extubation criteria: adequate spontaneous breathing with tidal volume >6 mL/kg, respiratory rate 12–25 breaths/min, sustained head lift for ≥5 s, stable hemodynamics without excessive vasoactive support, oxygen saturation ≥95% on FiO2 ≤0.4, and alertness sufficient to follow simple verbal commands. Cognitive behavior was assessed using the SOMCT (score ranging from 0 to 28, with higher scores indicating better cognitive function) by an anesthesiologist blind to the anesthetic strategy at 15 min after extubation. Recovery complications included agitation, shivering, hypoxemia and PONV during the recovery period. Agitation was assessed using Richmond Agitation Sedation Scale (score ≥1 points were defined as agitation). Hypoxemia was defined as oxygenation index≤300 mmHg. PONV was assessed with a four-point verbal rating scale.
Additionally, changes in lactate (Lac), pH, base excess (BE), and serum magnesium (Mg2+) concentrations were assessed at each time point. Parameters including Lac, pH and BE were examined by arterial blood gas analysis using GEM 3500. These measurements were taken before liquid therapy (T0), 2 h after operation began (T1), at the end of operation (T2), and 0.5 hour after extubation (T3). The serum ion concentration of magnesium was assessed at T0 and first day post-surgery (T4).
Sample Size and Statistical Analysis
Our pre-experimental results showed a difference of 3 min in the emergence time assuming a standard deviation of 5 min. Consequently, we estimated a sample size of 90 patients, with 45 in each group. The test power was established at 80% and the two-side α level was set at 0.05. Considering the 10% dropout rate, 100 patients (50 in each group) should be enrolled in this study.
The primary outcome was analyzed on both the intention-to-treat (ITT) population and the per-protocol (PP) population. For the other outcomes, an ITT analysis was performed. The Kolmogorov–Smirnov test was employed to assess the normality of distribution for continuous variables. Normally distributed continuous variables were presented as mean ± standard deviation and analyzed using the independent sample t-test for between-group comparisons. Lac, pH, BE and Mg2⁺ concentrations were assessed by repeated-measures analysis of variance (ANOVA) to compare the two groups across multiple time points. Post hoc pairwise comparisons were conducted with Bonferroni adjustment to identify specific intergroup and temporal differences. Non-normally distributed continuous variables were expressed as median (interquartile range) and analyzed using the Mann–Whitney U-test. The Hodges–Lehmann estimator was used to calculate the median difference together with its 95% confidence interval as the nonparametric effect size. Categorical variables were reported as frequency (percentage) and analyzed via the Pearson’s test or Fisher’s exact test, as appropriate. P < 0.05 was considered statistically significant.
Results
Patient Flow and Baseline Characteristics
After eligibility screening, 107 patients scheduled to undergo supratentorial tumor resection under general anesthesia were assessed for participation. A total of 100 patients were ultimately randomized to either the BRS group or the LRS group and were included in the ITT analysis. In the BRS group, one surgical duration were less than 3 hours and one patient experienced intraoperative massive blood loss, resulting in 48 patients included in the PP analysis. In the LRS group, one surgical duration were less than 3 hours and two patients experienced intraoperative massive blood loss, yielding 47 patients in the PP analysis (Figure 1).
Figure 1.
Study flow chart of participant screening, randomization and analysis.
Abbreviations: LRS, Lactate Ringer’s solution; BRS, sodium bicarbonate Ringer’s solution; ITT, intention-to-treat; PP, per-protocol.
Baseline demographic and clinical characteristics were well balanced and showed no statistically significant differences between the two groups (Table 1). In addition, intraoperative parameters, including operative duration, fluid infusion volume, blood loss, urine output, blood transfusion volume, propofol consumption, remifentanil consumption, sufentanil consumption, brain relaxation status, and incidence of intraoperative hemodynamic events, were also comparable between the two groups (Table 2).
Table 1.
Demographics and Clinical Characteristics
| Features | LRS (n=50) | BRS (n=50) | P Value |
|---|---|---|---|
| Age, y | 48.7±8.3 | 49.5±7.9 | 0.615 |
| BMI, kg/m2 | 25.4±1.8 | 25.5±1.8 | 0.836 |
| ASA (n, %) | 0.766 | ||
| I | 18 (36) | 16 (32) | |
| II | 30 (60) | 30 (60) | |
| III | 2 (4) | 4 (8) | |
| Sex, male (n, %) | 32 (64) | 30 (60) | 0.68 |
| Tumor classification (n, %) | 0.730 | ||
| Glioma high grade | 16 (32) | 17 (34) | |
| Glioma low grade | 2 (4) | 4 (8) | |
| Meningioma | 31 (62) | 27 (54) | |
| Metastasis | 1 (2) | 2 (4) | |
| Tumor site (n, %) | 0.767 | ||
| Frontal | 20 (40) | 25 (50) | |
| Parietal | 6 (12) | 4 (8) | |
| Temporal | 12 (24) | 13 (26) | |
| Occipital | 4 (8) | 3 (6) | |
| Others | 8 (16) | 5 (10) | |
| SOMCT score | 26 (24, 28) | 26 (25, 28) | 0.4 |
| Comorbidities (n, %) | |||
| Hypertension | 11 (22) | 12 (24) | 0.812 |
| Diabetes | 3 (6) | 2 (4) | 1 |
| Hypertension and diabetes | 1 (2) | 2 (4) | 1 |
| Rheumatoid arthritis | 0 (0) | 1 (2) | 1 |
Notes: Data are presented as mean±SD, median (IQR), or number (%).
Abbreviations: BMI, body mass index; ASA, American Society of Anesthesiologists; SOMCT, short orientation memory concentration test; LRS, Lactate Ringer’s solution; BRS, sodium bicarbonate Ringer’s solution.
Table 2.
Intraoperative Data
| Variables | LRS (n=50) | BRS (n=50) | P Value |
|---|---|---|---|
| Surgery duration, min | 279.2±55.6 | 265.9±44.8 | 0.192 |
| Total infusion volume, mL | 1900 (1600, 2425) | 2200 (1700, 2700) | 0.129 |
| Blood loss, mL | 250 (240, 270) | 250 (240, 280) | 0.726 |
| Urine volume, mL | 1000 (900, 1600) | 1350 (900, 1800) | 0.153 |
| Blood transfusion (n, %) | 3 (6) | 2 (4) | 1.000 |
| Propofol consumption, mg | 1020 (830, 1400) | 1150 (910,1640) | 0.118 |
| Remifentanil consumption, ug | 1650 (1300, 2200) | 1650 (1350, 2375) | 0.654 |
| Sufentanil consumption, ug | 35 (30, 40) | 37 (32, 41) | 0.294 |
| Brain Relaxation (n, %) | 0.509 | ||
| 1–2 (excellent or good) | 37 (74) | 34 (68) | |
| 3–4 (fair or poor) | 13 (26) | 16 (32) | |
| Intraoperative hemodynamic events (n, %) | |||
| Hypotension | 16 (32) | 18 (36) | 0.673 |
| Bradycardia | 7 (14) | 8 (16) | 0.779 |
| Hypertension | 9 (18) | 8 (16) | 0.79 |
| Tachycardia | 10 (20) | 11 (22) | 0.806 |
Notes: Data are presented as mean±SD, median (IQR), or number (%).
Abbreviations: LRS, Lactate Ringer’s solution; BRS, sodium bicarbonate Ringer’s solution.
Primary Outcome
In the ITT analysis (n = 100), patients in the BRS group exhibited a significantly shorter emergence time than those in the LRS group (13 min vs 16 min; median difference = 3, 95% CI: 1–4; P = 0.003). A consistent difference was observed in the PP analysis (n = 95, 13 min vs 16 min; median difference = 3, 95% CI: 1–4; P = 0.003) (Table 3).
Table 3.
Primary and Secondary Outcomes
| Variables | LRS (n=50) | BRS (n=50) | Median Difference or RR (95% CI) |
p Value |
|---|---|---|---|---|
| Emergence time, min | ||||
| ITT analysis | 16 (14, 18) | 13 (11, 16.25) | 3 (1, 4) | 0.003 |
| PP analysis | 16 (14.5, 18) | 13 (11, 16) | 3 (1,4) | 0.003 |
| Extubation time, min | 18.5 (15.75,20) | 15 (13.75, 18) | 2 (1, 4) | 0.010 |
| SOMCT score (15 min after extubation) | 25 (23, 27) | 25 (24, 27) | 0 (−1, 1) | 0.684 |
| Recovery complications (n, %) | ||||
| Agitation | 9 (18) | 7 (14) | 1.29 (0.52, 3.18) | 0.585 |
| Shivering | 4 (8) | 3 (6) | 1.33 (0.31, 5.65) | 1.000 |
| PONV | 7 (14) | 10 (20) | 0.7 (0.29, 1.69) | 0.424 |
| Hypoxemia | 1 (2) | 1 (2) | 1 (0.06, 15.75) | 1.000 |
| Total length of hospital stay, d | 12 (10, 14) | 12 (10, 13) | 0 (−1, 1) | 0.821 |
Notes: Data are presented as median (IQR), or number (%). For continuous variables, between-group differences are presented as median differences with 95% confidence intervals (CIs) calculated from the Hodges–Lehmann estimator. For categorical variables, between-group comparisons are presented as risk ratios (RRs) with 95% CIs.
Abbreviations: SOMCT, short orientation memory concentration test; PONV, postoperative nausea and vomiting; RR, risk ratio.
Secondary Outcomes
For the ITT population (n = 100), patients in the BRS group had a shorter extubation time relative to the LRS group (15 min vs 18 min; median difference = 2, 95% CI: 1 to 4; P = 0.01). No statistically significant intergroup differences were found in SOMCT scores at 15 min after extubation, postoperative complications during the recovery period, and total length of hospital stay (P > 0.05) (Table 3).
Other Outcomes
Repeated-measures ANOVA revealed a significant group-by-time interaction for lactate (F = 5.564, P = 0.004). Post-hoc pairwise comparisons with Bonferroni adjustment showed that lactate levels were significantly lower in Group BRS than in Group LRS at T2 and T3 (P < 0.05), and lactate levels were significantly elevated relative to baseline values in both groups at these two time points (P < 0.05) (Figure 2A).
Figure 2.
Comparison of Lac, pH, BE, and Mg2+ concentrations between two groups of patients at different time points.
Notes: Lactate (A), pH (B), base excess (C), and Mg2+ (D) concentrations at different time points in the two groups; intention-to-treat analysis (n = 100). Panels (A–C): Data are presented as mean±SD. Panel (D) Data are shown as median (horizontal lines) with 25 th to 75 th percentiles (box), mean (+ symbols), and minimum to maximum values (whiskers). T0:before liquid therapy, T1: 2 h after operation began, T2: at the end of operation, T3: 0.5 h after extubation, T4: on the first postoperative day. Compared with T0 in Group LRS, *P<0.05; Compare with T0 in Group BRS, # P<0.05; Compared with Group LRS, ** P<0.05.
Abbreviations: Lac, lactate; BE, base excess; LRS, Lactate Ringer’s solution; BRS, sodium bicarbonate Ringer’s solution.
However, the group-by-time interaction was not significant for pH (F = 0.547, P = 0.633), base excess (F = 0.633, P = 0.594), and Mg2⁺ concentrations (F = 3.511, P = 0.064), suggesting that the magnitude of change over time was comparable between the two groups. pH showed a significant main effect of group (F = 4.363, P = 0.039), reflecting higher time-averaged pH values across all time points in the BRS group. The main effect of group was non-significant for base excess (F = 1.626, P = 0.205) and Mg2⁺ concentrations (F = 0.847, P = 0.360). Bonferroni-adjusted within-group comparisons against baseline revealed a significant pH reduction in the LRS group and significant BE reductions in both groups after initiation of fluid therapy (P < 0.05), while pH in the BRS group did not change significantly at T1 and T2 relative to baseline (P > 0.05). Mg2⁺ concentrations decreased significantly on the first postoperative day (T4) in both groups (P < 0.05) (Figure 2B–D).
Discussion
In this randomized controlled trial, we demonstrated that intraoperative infusion of BRS significantly shortens the emergence time in patients undergoing supratentorial tumor resection when compared with LRS. In addition, patients receiving intraoperative BRS had earlier tracheal extubation and more stable intraoperative lactate levels. No significant between-group differences were observed in the remaining perioperative indicators.
High-quality randomized controlled trials (RCTs) focusing on intraoperative fluid selection for neurosurgical procedures remain scarce. Current guidelines recommend use of isotonic solutions rather than hypotonic solutions, considering the risk of oedema in neurosurgical population.6 In this study, we used slightly hypotonic solution as the control group and buffered isotonic solution as the experimental group. However, there was no significant differences between groups in terms of the safety outcomes. One prior RCT also showed that compared with BRS, LRS infusion did not aggravate cerebral edema in patients with traumatic brain injury, and short-term prognosis was comparable between the two groups.19 This outcome is not surprising, as both groups received routine intraoperative administration of mannitol and corticosteroid. Furthermore, existing evidence-based recommendations are limited by high heterogeneity among studies, which mainly enroll patients with different types of elective and emergency cerebral conditions.
Previous studies revealed that intraoperative infusion of BRS accelerates anesthesia emergence in bariatric surgery via maintaining internal homeostasis.15 In liver transplantation, it better stabilizes blood lactate levels and promotes postoperative recovery compared with LRS.14 Consistently, our study demonstrated shorter emergence and extubation time in patients who received BRS during supratentorial neurosurgery. This superiority could be explained by the followings. Firstly, BRS has benefits in reducing perioperative inflammation (eg, S100β, NSE), thereby improving patient emergence.20 Intracranial surgery usually involves significant surgical stimulation, neuro-inflammatory response and oxidative stress, all of which contribute to the delayed awareness.21 In contrast, administration of BRS can reduce this effect by reducing pro-inflammatory cytokines and endothelial glycocalyx degradation.20,22 We speculate that a similar neuroprotective and anti-inflammatory effect contributes to the improved emergence profile observed in our study. Moreover, we hypothesize that the accelerated recovery may be partially attributed to enhanced anesthetic metabolism. Compared with LRS, BRS provides better hepatic and renal functional protection, which may accelerate the clearance of various anesthetics and consequently promote postoperative recovery. Lastly, there is a potential possibility linked with the lactate-stabilizing effect of BRS. Perioperative hyperlactatemia without acidosis is frequently observed in patients with intracranial pathologies and may provoke inflammatory responses.23 Meanwhile, high lactate/glucose ratios might contribute to central fatigue and cognitive impairment during neuroinflammation,24 further impair neurological functional recovery and prolong the emergence time. Recent studies have shown BRS infusion could significantly improve the recovery along with the observed better LAC metabolism and acid-base balance compared with other crystalloid solutions in gastrointestinal surgery. In our study, we found the lactate level in the BRS group was significantly lower than that in the LRS group at the end of surgery and 0.5 h after extubation, reaffirming the blood lactate reduction effect of BRS in neuroanesthesia. We hypothesize that the low systemic lactate environment induced by BRS infusion may attenuate high intracerebral lactate concentrations, thereby facilitating the recovery of consciousness. To date, although the adverse effects of elevated lactate without acidosis for brain tumor surgery remain inconclusive,5,23 there are consistent indications that elevated lactate comes with prolonged hospital admission and higher healthcare costs.
Previous studies have reported BRS can better maintain pH status and correct metabolic acidosis in perioperative patients.25,26 Following liver transplantation reperfusion or perforation peritonitis, the pH and BE values changed obviously in Group LRS, whereas the change in Group BRS was gradual.14,26 While Zhou, et al found there is no significant difference observed in pH, BE, and electrolyte levels (K+, Na+, Cl−, Ca2+) between the two solutions during long-term open abdominal surgeries.27 Our results demonstrated parallel temporal trajectories for pH and BE, indicating comparable temporal changes in these variables in the two groups. BRS was associated with higher time-averaged pH, whereas no group difference was found for BE, implying that any beneficial effect of BRS on acid-base balance during supratentorial tumor resection was modest. This inconsistency likely due to the difference between routine surgical and critically ill patients alongside divergent physiological differences. Therefore, BRS may offer acid-base balance stability for critically ill patients undergoing shock and liver surgery, particularly in the cases of severe ischemia and hypoxia.26,28
Magnesium has long been recognized as a promising neuroprotective agent, and serum magnesium concentrations often decline after intracranial surgery.17,29 Consistent with prior reports, serum magnesium concentrations decreased to variable extents under both infusion regimens in our study. The group-by-time interaction for magnesium was marginally significant (P = 0.064), suggesting a trend toward differing temporal trajectories between the two groups that did not meet the conventional threshold for statistical significance. This marginal trend may be attributed to the limited sample size. Previous studies of laparoscopic hemihepatectomy reported that BRS compensates for intraoperative magnesium loss, yielding higher postoperative magnesium concentrations relative to LRS.25 However, those findings cannot be directly extrapolated to patients at high risk of magnesium depletion, particularly those with disrupted cerebral homeostasis. Since magnesium concentrations were not dynamically measured intraoperatively or in the immediate postoperative period, we cannot definitively determine whether BRS infusion slows the rate of magnesium decline in patients undergoing intracranial surgery.
This study has several limitations. First, the study lacked measures of cerebral, hepatic and renal injury biomarkers, which prevented further exploration of the mechanisms linking intraoperative fluid infusion to postoperative emergence. Second, potential performance bias existed because attending anesthesiologists were unblinded to group allocation, but the investigators who assessed recovery outcomes were blinded. Finally, extending our findings to other groups was further constrained because it was a single-center study with detailed inclusion and exclusion criteria. Thus, further multicenter, large sample randomized controlled trials are warranted to compare the effects of LRS and BRS on internal environment and emergence time in supratentorial neurosurgery, and to clarify the underlying mechanisms.
Conclusion
Patients receiving BRS during supratentorial tumor resection exhibited faster emergence from anesthesia, earlier extubation and lower lactate levels during recovery, yet SOMCT scores at 15 min after extubation and complication rates showed no significant differences compared with patients receiving LRS.
Funding Statement
This study was supported by Scientific Research Program of 904th Hospital (ZZ202304), Top talent support program for young and middle-aged people of Wuxi Health Committee (BJ2023110).
Abbreviations
LRS, Lactated Ringer’s solution; BRS, Bicarbonate Ringer’s solution; ITT, intention-to-treat; PP, per-protocol; ASA, American Society of Anesthesiologists; BMI, body mass index; BIS, bispectral index; CO, cardiac output; SVV, stroke volume variation; EtCO2, end - tidal carbon dioxide; PONV, postoperative nausea and vomiting, GDFT, goal-directed fluid therapy; MAP, mean arterial pressure; PACU, post-anesthesia care unit; Lac, lactate; BE, base excess; SOMCT, Short Orientation Memory Concentration Test; analysis of variance, ANOVA; RR, risk ratio.
Data Sharing Statement
The data presented in this study are available upon reasonable request from the corresponding author.
Ethics Approval and Informed Consent
This study was approved by the Ethics Committee of the 904th Hospital of the Joint Service Support Force of the Chinese People’s Liberation Army (Ethics Approval No. 20250603) and was registered in the Chinese Clinical Trial Registry (ChiCTR2500105691). Every patient provided written informed consent before enrollment. This study was conducted in accordance with the Declaration of Helsinki.
Author Contributions
All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article. All authors gave final approval of the version to be published, have agreed on the journal to which the article has been submitted, and agree to be accountable for all aspects of the work.
Disclosure
The authors declare no conflicts of interest in this work.
References
- 1.Van Der Boog ATJ, Rados M, Akkermans A, et al. Occurrence, Risk Factors, and Consequences of Postoperative Ischemia After Glioma Resection: a Retrospective Study. Neurosurgery. 2023;92(1):125–11. doi: 10.1227/neu.0000000000002149 [DOI] [PubMed] [Google Scholar]
- 2.Berger A, Tzarfati GG, Serafimova M, et al. Risk factors and prognostic implications of surgery-related strokes following resection of high-grade glioma. Sci Rep. 2022;12(1):22594. doi: 10.1038/s41598-022-27127-5 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Wang P, Ouyang Y, You Q, et al. Associations between intraoperative hypotension and postoperative seizures following craniotomy for brain tumor resection. J Clin Anesth. 2026;112:112201. doi: 10.1016/j.jclinane.2026.112201 [DOI] [PubMed] [Google Scholar]
- 4.Khozenko A, Lamperti M, Velly L, et al. Role of anaesthesia in neurosurgical enhanced recovery programmes. Best Pract Res Clin Anaesthesiol. 2021;35(2):241–253. doi: 10.1016/j.bpa.2020.11.001 [DOI] [PubMed] [Google Scholar]
- 5.Klimek M, De Smalen P, Janssen J. Hyperlactatemia and other perioperative metabolic disturbances in neuroanesthesia. Curr Opin Anaesthesiol. 2022;35(5):537–542. doi: 10.1097/ACO.0000000000001180 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Ostermann M, Auzinger G, Grocott M, et al. Perioperative fluid management: evidence-based consensus recommendations from the international multidisciplinary PeriOperative Quality Initiative. Br J Anaesth. 2024;133(6):1263–1275. doi: 10.1016/j.bja.2024.07.038 [DOI] [PubMed] [Google Scholar]
- 7.Bampoe S, Odor PM, Dushianthan A, et al. Perioperative administration of buffered versus non-buffered crystalloid intravenous fluid to improve outcomes following adult surgical procedures. Cochrane Database Syst Rev. 2017;9(9):Cd004089. doi: 10.1002/14651858.CD004089.pub3 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Shin CH, Long DR, Mclean D, et al. Effects of Intraoperative Fluid Management on Postoperative Outcomes: a Hospital Registry Study. Ann Surg. 2018;267(6):1084–1092. doi: 10.1097/SLA.0000000000002220 [DOI] [PubMed] [Google Scholar]
- 9.Vignarajah M, Berg A, Abdallah Z, et al. Intraoperative use of balanced crystalloids versus 0.9% saline: a systematic review and meta-analysis of randomised controlled studies. Br J Anaesth. 2023;131(3):463–471. doi: 10.1016/j.bja.2023.05.029 [DOI] [PubMed] [Google Scholar]
- 10.Ha Y, Rajani K, Riviere-Cazaux C, et al. An Injury-like Signature of the Extracellular Glioma Metabolome. Cancers. 2024;16(15):2705. doi: 10.3390/cancers16152705 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Bharadwaj S, Venkatraghavan L. Serum Lactate is a Biomarker of Brain Tumor Metabolism. J Neurosurg Anesthesiol. 2017;29(4):469. doi: 10.1097/ANA.0000000000000382 [DOI] [PubMed] [Google Scholar]
- 12.Salinero A, Mitzova-Vladinov G. Battle of the Crystalloids in the Operating Room: a Literature Review. J PeriAnesthesia Nurs. 2021;36(6):629–637. doi: 10.1016/j.jopan.2021.03.012 [DOI] [PubMed] [Google Scholar]
- 13.Andersen LW, Mackenhauer J, Roberts JC, et al. Etiology and Therapeutic Approach to Elevated Lactate Levels. Mayo Clin Proc. 2013;88(10):1127–1140. doi: 10.1016/j.mayocp.2013.06.012 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Xian H, Xie Q, Qin K, et al. Effect of Sodium Bicarbonate Ringer’s Solution on Intraoperative Blood Gas Analysis and Postoperative Recovery Time in Liver Transplantation: a Single-Center Retrospective Study. Ann Transplant. 2023;28:e939097. doi: 10.12659/AOT.939097 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Jiang X, Wang R, Guo L, et al. Effects of Sodium Bicarbonate Ringer’s Solution Combined with Positive End-Expiratory Pressure on the Internal Environment of Patients Undergoing Bariatric Surgery: a Randomized 2 × 2 Factorial Design Pilot. Obes Surg. 2025;35(1):239–248. doi: 10.1007/s11695-024-07631-5 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Liu J, Gao Y, He Z, et al. The efficacy of sodium bicarbonated Ringer’s solution versus lactated Ringer’s solution in elderly patients undergoing gastrointestinal surgery: a prospective randomized controlled trial. Am J Transl Res. 2023;15(8):5216–5227. [PMC free article] [PubMed] [Google Scholar]
- 17.Marelli S, Querci L, Chieregato A. Magnesium in Neurocritical Care: clinical Relevance, Status Assessment, and Practical Implications for Outcomes-A Narrative Review. Nutrients. 2026;18(9). doi: 10.3390/nu18091359 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Dey A, Bidkar PU, Swaminathan S, et al. Comparison of two techniques of goal directed fluid therapy in elective neurosurgical patients - a randomized controlled study. Br J Neurosurg. 2025;39(1):23–31. doi: 10.1080/02688697.2023.2173722 [DOI] [PubMed] [Google Scholar]
- 19.Hui Y, Tan S, Ding G, et al. Effect of sodium bicarbonate ringer’s solution on early renal function and prognosis of patients with traumatic brain injury after surgery: a single-center randomized controlled clinical study. J Clin Anesth. 2026;112:112226. doi: 10.1016/j.jclinane.2026.112226 [DOI] [PubMed] [Google Scholar]
- 20.Wang H, Lin C, Zhang W, et al. Effect of acute hypervolemic hemodilution with bicarbonated Ringer’s solution on perioperative S100β and NSE in elderly patients undergoing spine surgery. Biotechnol Genet Eng Rev. 2024;40(4):4849–4861. doi: 10.1080/02648725.2023.2216970 [DOI] [PubMed] [Google Scholar]
- 21.Kehlet H. Enhanced postoperative recovery: good from afar, but far from good? Anaesthesia. 2020;75(Suppl 1):e54–e61. doi: 10.1111/anae.14860 [DOI] [PubMed] [Google Scholar]
- 22.Shi Y, Shi Y, Tao Y, et al. Intraoperative Use of Sodium Bicarbonate Ringer’s Solution Instead of Sodium Lactate Ringer’s Solution to Reduce Endothelial Glycocalyx Degradation and Improve Postoperative Recovery During Cardiopulmonary Bypass Cardiac Surgery: a Single-Center Prospective Cohort Study. Drug Des Devel Ther. 2024;18:5881–5893. doi: 10.2147/DDDT.S501657 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.De Smalen PP, Van Ark TJ, Stolker RJ, et al. Hyperlactatemia After Intracranial Tumor Surgery Does Not Affect 6-Month Survival: a Retrospective Case Series. J Neurosurg Anesthesiol. 2020;32(1):48–56. doi: 10.1097/ANA.0000000000000594 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Zhang L, Liu J, Miao Z, et al. The Association of Fructose Metabolism With Anesthesia/Surgery-Induced Lactate Production. Anesth Analg. 2025;140(3):710–722. doi: 10.1213/ANE.0000000000007350 [DOI] [PubMed] [Google Scholar]
- 25.Song J, Liu Y, Li Y, et al. Comparison of bicarbonate Ringer’s solution with lactated Ringer’s solution among postoperative outcomes in patients with laparoscopic right hemihepatectomy: a single-centre randomised controlled trial. BMC Anesthesiol. 2024;24(1):152. doi: 10.1186/s12871-024-02529-2 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Chaudhary RK, Dhir A, Ganesh V, et al. Effect of isotonic sodium bicarbonate infusion on perioperative acid-base status among patients undergoing emergency laparotomy for perforation peritonitis (ISABEL trial): a randomized controlled trial. Eur J Trauma Emerg Surg. 2025;51(1):10. doi: 10.1007/s00068-024-02751-0 [DOI] [PubMed] [Google Scholar]
- 27.Zhou S, Zhao K, Liu C, et al. The Efficacy of Sodium Bicarbonate Ringer’s Solution and Lactate Ringer’s Solution in Patients Undergoing Long-Term Abdominal Open Surgery: a Multicenter Prospective Randomized Controlled Study. Drug Des Devel Ther. 2025;19:4617–4628. doi: 10.2147/DDDT.S514725 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Han SJ, Zhou ZW, Yang C, et al. Hemorrhagic, hypovolemic shock resuscitated with Ringer’s solution using bicarbonate versus lactate: a CONSORT-randomized controlled study comparing patient outcomes and blood inflammatory factors. Medicine. 2022;101(46):e31671. doi: 10.1097/MD.0000000000031671 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Song B, Jiang M, Zhang Y, et al. Research hotpots and frontier trends of neuroprotective effects of magnesium from 1999 to 2023: a bibliometric analysis. CNS Neurosci Ther. 2024;30(2):e14597. doi: 10.1111/cns.14597 [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data presented in this study are available upon reasonable request from the corresponding author.