A Correlational Study to Analyze the Effect of Decrease in Mean Arterial Pressure on Cerebral Oxygen Saturation in Hypertensive Patients during Hypotensive Anesthesia for Transsphenoidal Surgery

Abstract

Background

Controlled hypotension is employed for transsphenoidal surgeries (TSS) to provide a bloodless surgical field carries the potential risk of cerebral hypoperfusion and neurological injury. Pituitary adenoma may present with a high incidence of hypertension due to associated acromegaly and Cushing's disease. The risk of cerebral hypoperfusion increases with a decrease in blood pressure in chronic hypertensive patients due to a rightward shift of the autoregulation curve. This observational study aimed to correlate the changes in cerebral oxygenation (ScO₂) with reduction in mean arterial pressure (MAP) in hypertensive patients undergoing TSS to determine the safety limit of permissive hypotension.

Materials and Methods

Thirty hypertensive patients undergoing transsphenoidal pituitary surgery under hypotension anesthesia (targeted MAP 60–70 mm Hg) were included. Calibrated near-infrared spectroscopy was used to record continuous ScO₂. A decrease in the absolute value of ScO₂ <50 or ≥20% drop from baseline was considered significant. Patients were monitored after surgery for hemodynamic instability, cognitive dysfunction, and any neurological complications.

Results

Eleven out of 30 patients showed a significant drop in ScO_2. A decrease in MAP < 70 mm Hg or more than 30% from baseline was associated with a significant reduction in ScO₂. A fair positive correlation between decrease in MAP and drop in ScO₂ (rho = 0.6, p < 0.001) was observed. The duration of hypertension and ventricular hypertrophy was also associated with a decrease in ScO₂. Postoperative cognitive score was low on day 1 after surgery in patients having deceased ScO₂ (p = 0.045).

Conclusion

Our study showed that ScO₂ monitoring can play a pivotal role in managing MAP during hypotensive anesthesia. It can provide an early warning sign of decreased ScO₂, enabling rapid intervention to prevent postoperative neurological deficit.

Keywords

cerebral hypoxia - chronic hypertension - cognitive dysfunction - hypotensive anesthesia - near-infrared spectroscopy - pituitary surgery

Introduction

The transsphenoidal surgery (TSS) is the standard approach for excision of pituitary tumors that lie within the sella turcica and those that have extended to or originated in the immediate suprasellar area.[1] The endoscopic approach to the pituitary through the nasal septum not only improves visualization of the sella but also leads to significant reduction in operative time and length of hospital stay.[1] However, the anesthetic management of these patients is challenging due to associated Cushing's disease, acromegaly, or pheochromocytoma.[2] The prevalence of hypertension in functional pituitary tumors ranges from 35 to 80% in different clinical series, and most of these patients have associated ventricular hypertrophy.[3] The goals of anesthesia for endoscopic TSS include maintaining hemodynamic stability, optimizing cerebral oxygenation (ScO₂), providing adequate surgical exposure, and ensuring rapid smooth emergence to facilitate early neurological assessment.[4] [5]

Controlled hypotensive anesthesia is often used for endoscopic TSS to minimize intraoperative bleeding, improve the surgical field, and reduce the risk of complications.[6] However, recent evidence suggests that while this approach may offer benefits, it also carries the potential risks of cerebral hypoperfusion with decreasing cerebral blood flow (CBF), leading to postoperative neurological injury, such as neurocognitive disorders and stroke.[7] [8] The risks may be higher in chronic hypertensive patients due to altered autoregulation.[9] [10] However, no definitive threshold of intraoperative hypotension has been established for neurological complications.

The current prospective cohort study was planned to find out the safety limits of mean arterial pressure (MAP) reduction during permissive hypotension without compromising cerebral tissue oxygenation in hypertensive patients. The primary aim of this study was to correlate the change in cerebral tissue oxygenation (ScO₂) with decrease in MAP by using near-infrared spectroscopy (NIRS) in controlled hypertensive patients undergoing elective TSS. The secondary objective was to assess the risk of neurocognitive disorders and other neurological complications of hypotensive anesthesia in these patients. The NIRS noninvasively monitor ScO₂ and provide an estimation of normal CBF.[11] Normal ScO₂ value ranges from 60 to 80. Previous studies have shown that an absolute value of ScO₂ less than 50 or reduction of 20% from baseline value was associated with a higher risk for stroke and postoperative cognitive dysfunctions (POCD).[12] We hypothesize that continuous intraoperative monitoring of ScO₂ can assist in the timely diagnosis of insufficient ScO₂ during hypotensive anesthesia.

Materials and Methods

This study was conducted after obtaining ethics committee approval and registering the trial in the Clinical Trial Registry, India (CTRI/2020/01/022763; CTRI). After taking written informed consent, 30 adult hypertensive patients undergoing elective TSS for resection of pituitary tumor were enrolled for the study from February to November 2020 in a tertiary care hospital and research institute. The inclusion criteria were age between 18 and 65 years, American Society of Anesthesiologists physical status I to III, and the patients having well-controlled hypertension (systolic blood pressure ≤ 140 mm Hg and diastolic ≤ 90 mm Hg). Exclusion criteria were patients with ischemic cardiovascular disease, conduction defects, cerebrovascular disease, suspected neurological deficits, hepatic or renal insufficiency, altered mental state, and the patients receiving antipsychotic drugs or anticoagulant therapy. The patients were examined a day before surgery to assess their fitness for the proposed surgical procedure, and routine investigations such as complete hemogram, coagulation profile, electrocardiogram (ECG), and X-ray chest were performed. Minimental status examination (MMSE, 0–30, ≥24 indicates normal cognitive function)[13] was also performed preoperatively to assess the preoperative cognitive status of the patients. All patients were advised for fasting as per guidelines prior to surgery and were premedicated with a tablet alprazolam 0.25 mg orally at night before surgery.

Once the patient was shifted to the operating room, standard monitoring of ECG, heart rate (HR), noninvasive blood pressure, and oxygen saturation (SpO₂) were started. The NIRS sensors were applied on both sides of the forehead just prior to the administration of general anesthesia, and baseline values of ScO₂ were recorded. After preoxygenation, intravenous (IV) fentanyl 2 µg kg⁻¹ was given. Induction of anesthesia was done with titrating doses of propofol 1 to 2 mg kg⁻¹ IV till the loss of response to verbal command, followed by vecuronium 0.1 mg kg⁻¹ IV for achieving muscle relaxation and smooth intubation. Anesthesia was maintained with desflurane and air–oxygen mixture with fraction of inspired oxygen = 0.4. After intubation of the trachea with an appropriately sized endotracheal tube, the patients were mechanically ventilated keeping the end-tidal carbon dioxide (EtCO₂) between 35 and 40 mm Hg. An arterial cannula was inserted in the left radial artery to monitor intra-arterial blood pressure. Transesophageal temperature was recorded and maintained within normal limits. Patients received 0.9% normal saline at the rate of 4 to 6 mL kg⁻¹ h⁻¹ during the intraoperative period.

For achieving controlled hypotension, dexmedetomidine infusion was started with a loading dose of 1 µg kg⁻¹ over 10 minutes followed by a maintenance dose of 0.2 to 1.0 µg kg⁻¹ h⁻¹. The target value for achieving controlled hypotension was reduction in MAP till 60 to 65 mm Hg. Patients' HR, intra-arterial blood pressure, SpO₂, temperature, EtCO₂, and ScO₂ were monitored continuously and recorded at baseline, after intubation, at the start of dexmedetomidine infusion, and then every 5 minutes till the end of surgery. A decrease in the ScO₂ by 20% from baseline or a decrease in the absolute value of <50 was considered a significant drop in ScO₂. The lowest tolerated MAP at which ScO₂ deteriorated was recorded, and the patient was treated by reducing/stopping dexmedetomidine infusion and administration of IV fluids and phenylephrine to achieve the normal levels of ScO₂ as per the attending anesthesiologist's discretion. Arterial blood gas analysis was done before starting dexmedetomidine infusion, at the end of surgery, and in between whenever required. Intraoperative blood loss and urine output were recorded.

All patients received IV paracetamol 15 mg kg⁻¹ at the end of surgery during the removal of the nasal endoscope ondansetron (4 mg IV) was administered at the same time to prevent postoperative nausea and vomiting (PONV). Dexmedetomidine infusion was stopped 10 to 15 minutes before the end of surgery (just after resection of tumor). The surgical field bleeding was graded by the surgeon using the Boezaart's scale consisting of grades 1 to 5, grade < 4 was considered as surgeon's satisfaction.[14] At the end of surgery, patient's lungs were ventilated with 100% oxygen, and tracheal extubation was performed after the complete reversal of the neuromuscular blockade.

Patients were monitored for 24 hours after surgery for hemodynamic instability, pain, urine output, PONV, and any other complications in the postanesthesia care unit or neurosurgical ward. All patients received paracetamol 15 mg kg⁻¹ IV at 6-hour intervals for postoperative pain relief. Pain score was assessed at 2, 6, 12, and 24 hours postoperatively by numeric rating scale (NRS, 0–10, 0 = no pain and 10 = maximum tolerable pain). If the patients complained of pain with NRS >3, the rescue analgesic fentanyl 1 µg kg⁻¹ was given. Patients having severe nausea or vomiting received metoclopramide 10 mg IV. The POCD was assessed on the day after surgery and then at seventh postoperative day by using MMSE. A score of less than 24/30 was considered deterioration in the mental status of the patient.

Statistical Analysis

Statistical analysis was performed using SPSS 22.0 software. Spearman's correlation analysis was used to determine the correlation between MAP and ScO₂. Receiver operating characteristic (ROC) curve analysis was applied to find out the cutoff value of MAP to predict significant decrease in cerebral SpO₂ during controlled hypotensive anesthesia. Mann–Whitney's U test was applied to compare categorical variables such as pain score, surgical field grading, and MMSE. Subgroup analysis was also performed to find out the other factors responsible for cerebral desaturation in hypertensive patients. A two-tailed p-value <0.05 was considered statistically significant with a 95% confidence interval (CI).

The sample size was calculated using the expected correlation coefficient (r) value of 0.5, power of 80%, and two-tailed α value of 0.05. A total of 29 patients were required to determine a significant correlation.

Results

Total 36 patients were recruited, out of which 6 patients were excluded due to high blood pressure on the day of surgery or intraoperative surgical complications leading to open craniotomy. A total of 30 patients were enrolled in the study and analyzed. The ScO₂ values were recorded from both the sides of the brain and the average was calculated. There was significant drop in ScO₂ (≥20% from baseline) in 11 out of 30 patients during intraoperative period. At significant drop in ScO₂, the mean MAP was recorded as (median, interquartile range [IQR]) 68 (65–69.5) mm Hg.

Spearman's Correlation Analysis

There was a moderate positive correlation between MAP (mm Hg) and maximum drop in ScO₂ (rho = 0.5, p < 0.004) ([Fig. 1a]). It showed that a reduction in MAP < 70 mm Hg might lead to >20% decrease in ScO₂. A significant positive correlation was also detected between the percent change in MAP and the maximum drop in ScO₂ (rho = 0.6, p < 0.001) which showed that >30% reduction in MAP from baseline might lead to a significant drop in ScO₂ ([Fig. 1b]). On multivariate analysis, a moderate negative correlation was observed between the duration of hypertension and the maximum drop in ScO₂ (rho = 0.49, p = 0.006) showing that the possibility of significant decrease in ScO₂ increases with longer duration of hypertension (>5 years) ([Fig. 2]).

Fig. 1 (a) Correlation between decrease in MAP (mm Hg) and maximum drop in ScO₂ (n = 30), rho = 0.5, p < 0.004. (b) Correlation between reduction (in percent) in MAP (mm Hg) from baseline and maximum drop in ScO₂ (n = 30), rho = 0.6, p < 0.001. MAP, mean arterial pressure; ScO₂, cerebral oxygenation.

Fig. 2 Correlation between duration of hypertension and maximum drop in ScO₂ (n = 30), rho = − 0.49 (negative correlation), p < 0.006.ScO₂, cerebral oxygenation

Receiver Operating Characteristic Curve Analysis

The area under the ROC curve for percent change in MAP (mm Hg) at the maximum drop in ScO₂ predicting a significant saturation drop was 0.751 (95% CI: 0.571–0.932, p = 0.025). At 32.67% reduction in MAP from baseline, a significant ScO₂ drop (>20% of baseline) was predicted with a diagnostic accuracy of 73.3% (sensitivity 72.7% and specificity 73.7%). The odds ratio (OR) was 7.47 (95% CI: 1.4–39.84), and the relative risk (RR) was 3.49 (95% CI: 1.27–10.56) for a significant drop in ScO₂. The positive predictive value (PPV) of MAP for predicting a significant drop in ScO₂ was 61.5%, and the negative predictive value (NPV) was 82.4% ([Fig. 3]).

Fig. 3 ROC curve analysis showing diagnostic performance of reduction in MAP (mm Hg) from baseline in predicting a significant drop in ScO₂ (n = 30). MAP, mean arterial pressure; ROC, receiver operating characteristic; ScO₂, cerebral oxygenation.

The surgical field grading was satisfactory in all the patients (grade 3 or less than 3). The pain scores were higher during the early postoperative period and required rescue analgesia with IV fentanyl. None of the patients had severe nausea or vomiting. No perioperative complications including stroke, acute renal failure and myocardial infarction, bleeding, deterioration of neurological status, and signs of meningism were observed in any of the patients. The median MMSE scores were (median [IQR]) 26 (25.5–28) and 27 (26–29) at postoperative days 1 and 7, respectively.

On subgroup analysis, the demographic variables were comparable among the patients showing significant drop in ScO₂ (ScO₂+ group) and normal ScO₂ patients (ScO₂− group), except the duration of hypertension (longer in the ScO₂+ group as compared with the ScO₂− group, p = 0.008), and left ventricular hypertrophy (LVH) changes in ECG ([Table 1]). There was no significant difference in the duration of anesthesia and the requirement of dexmedetomidine between the two groups. The groups were also comparable in terms of total blood loss and intraoperative fluid administration. However, the maximum decrease in ScO₂ was significantly more in the ScO₂+ group as compared with ScO₂− group (−23.84 vs. −11.32%, p < 0.001) ([Fig. 4]). The mean MAP at maximum drop in ScO₂ was 68.27 ± 6.48 and 73.32 ± 5.70 mm Hg in the ScO2+ group and ScO₂− group, respectively (p = 0.04). The decrease in MAP from baseline was also significantly more in ScO₂+ group than in the ScO₂− group (p = 0.025) ([Table 1]). The two groups were comparable in terms of HR at any time point. There was no episode of bradycardia (HR <40 bpm) in any group of patients. The MMSE cognitive score was significantly lower at postoperative day 1 in the ScO₂+ group (median [IQR]: 25[24-26]) as compared with ScO₂− group (median [IQR]: 28 [27–29]) (p = 0.045), while it was comparable between the two groups at seventh postoperative day (p = 0.072).

Fig. 4 Line diagram showing the change in ScO₂ over time in ScO₂+ and ScO₂− patients. ScO₂, cerebral oxygenation.

Table 1 Comparison of demographic data and hemodynamic parameters at the maximum drop in ScO₂ in both subgroups

Parameters	ScO2+ (n = 11)	ScO2− (n = 19)	p-Value
Age (y)	55.82 ± 11.91	50.42 ± 8.76	0.189
Male: female	5:6	11:8	0.510
Duration of hypertension (mo)	59.91 ± 31.35	21.11 ± 21.09	0.008
Left ventricular hypertrophy, n (%)	9 (81.8%)	3 (15.8%)	0.001
Duration of anesthesia (min)	171.82 ± 27.14	173.68 ± 29.29	0.926
Dexmedetomidine dose (µg kg−1 h−1)	0.43 ± 0.20	0.47 ± 0.16	0.257
Total blood loss (mL)	157.73 ± 19.15	160.79 ± 31.10	0.769
Maximum drop in ScO2 (%)	− 23.84 ± 2.73	− 11.32 ± 6.53	< 0.001
MAP at maximum drop in ScO2 (mm Hg)	68.27 ± 6.48	73.32 ± 5.70	0.040
% decrease in MAP (mm Hg) from baseline at maximum drop in ScO2	− 33.05 ± 4.77	− 26.28 ± 6.40	0.018

Abbreviations: MAP, mean arterial pressure; ScO₂, cerebral oxygenation.

Note: Data presented as mean ± standard deviation or no. of patients.

Discussion

Deliberately induced hypotension is one of the proposed techniques to produce a controlled and safe reduction in blood pressure while preserving CBF and organ perfusion to provide a bloodless surgical field in various endoscopic and microsurgical procedures.[15] In this technique, the MAP is usually maintained between 55 and 65 mm Hg based on the belief that this represents the lowest MAP at which autoregulation of CBF is still in action.[16]

Controlled hypotensive anesthesia has been employed in various neurosurgical procedures to reduce intraoperative bleeding and optimizing surgical conditions.[6] However, recent evidence suggests that while this approach may offer benefits, it also carries potential risks of enhancing neurological injury.[7] [8] Although transsphenoidal resection of pituitary tumors is generally considered a low-risk procedure for neuronal injury; the mechanical manipulation, direct injury, and compromise of perfusion to the posterior lobe may increase the risk of ischemic brain injury. A recent study by Hallén et al[17] demonstrated an increase in circulating brain injury biomarkers after endoscopic surgery for pituitary tumors with suprasellar extension. It has been proposed that manipulation of suprasellar neuronal structures during pituitary surgery may precipitate the neuronal injury. In another study, Thorsson et al[18] found that intraoperative hypotension during transsphenoidal pituitary surgery was associated with an increase in plasma levels of brain injury markers.

NIRS monitors regional cerebral tissue oxygenation and thus provides an indirect measure of CBF. NIRS values correlated well with the invasive monitors of ScO₂, including mixed venous and jugular bulb SpO₂.[19] Farzanegan et al[20] demonstrated a moderate cross correlation between the MAP and ScO₂ (r = 0.728, 95% CI: 0.56–0.88) in normotensive patients receiving controlled hypotensive anesthesia during functional endoscopic sinus surgery (FESS) and recommended maintaining MAP >55 mm Hg with intraoperative monitoring of ScO₂. In another study, Park et al[21] used hypotensive anesthesia in 30 controlled hypertensive patients during spine surgery targeting MAP between 55 and 65 mm Hg and found that the absolute ScO₂ values varied from 50 to 80 throughout the intraoperative period.

In the present study, the MAP was targeted between 60 and 65 mm Hg, and the ScO₂ varied from 50 to 75; total 11/30 (37%) patients showed more than 20% decrease in ScO₂ during the intraoperative period. The MAP at maximum ScO₂ drop was 68.27 ± 6.48 mm Hg, and the mean percentage decrease in MAP was ∼33.05 ± 4.77 from baseline. We found that a reduction in MAP less than 70 mm Hg or more than 30% from baseline might be associated with a significant reduction in ScO_2. The Spearman's correlation analysis demonstrated a moderate positive correlation between the decrease in MAP from baseline and the maximum drop in ScO₂ (rho = 0.6, p < 0.001). The ROC analysis also showed a significant (p = 0.025) diagnostic accuracy of MAP for predicting a drop in ScO₂ (PPV = 61.5%, NPV = 82.4%, OR = 7.47, RR = 3.49) with a sensitivity of 73% and a specificity of 74%.

We also found other factors contributing to a significant drop in ScO₂ including duration of hypertension and evidence of LVH on ECG. In the present study, ScO₂+ group patients had a longer duration of hypertension as compared with ScO₂− group (p < 0.008). About 82% of patients in the ScO₂+ group had evidence of LVH on ECG as compared with only 16% of patients in the ScO₂− group (p < 0.001). A moderate negative correlation between the duration of hypertension and the maximum drop in ScO₂ showed a higher possibility of a significant drop in ScO₂ with a duration of hypertension ≥ 60 months.

In a previous study, Ha et al[22] found that hypotensive anesthesia was an effective method to provide a bloodless surgical field in FESS and established a direct correlation between MAP and the bleeding assessment score (r = 0.36). In the present study, surgical field grading was up to the surgeon's satisfaction in all the patients.

Although there are weak recommendations regarding the use of hypotensive anesthesia in TSS, due to special concern for the disturbance in cerebral autoregulation in these patients, leading to higher postoperative neurocognitive and other complications. We also observed a lower cognitive score in the ScO₂+ group during the early postoperative period, though no other complications of hypotensive anesthesia, such as perioperative renal failure, stroke, and myocardial infarction, were observed in any patient. This might be because, due to continuous ScO₂ monitoring, the corrective measures to increase the MAP were taken immediately to avoid cerebral ischemia. In a randomized controlled trial on the patients undergoing lumbar spondylosis surgery under hypotensive anesthesia, Trafidło et al[23] also found that the patients in whom NIRS was used to monitor ScO₂ had better performance postoperatively as compared with those patients in whom NIRS was not used.

The main limitations of the study include a single-center observational study and being performed in only one type of surgery. The limitations involved in using NIRS, which include interference with skin pigment, external light source, and perspiration, also add to our study. Future, multicenter randomized controlled trials with a large sample size involving different types of surgeries are required before our results can be generalized.

Conclusion

In conclusion, the management of intraoperative blood pressure during TSS for pituitary adenoma is crucial for optimizing surgical conditions and patients' outcomes. Anesthetic technique selection should be individualized, considering patient-specific factors and comorbidities. While controlled hypotension may improve surgical conditions during TSS by reducing blood loss, it is associated with potential risks of postoperative organ injury. Judicious management of blood pressure with close intraoperative monitoring of ScO₂ is paramount to balance the clearer surgical field against the risks of hypotension-related complications.

Conflict of Interest

None declared.

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Publication History

Article published online:
29 April 2025