Efficacy of Dexmedetomidine versus Propofol in Patients Undergoing Endoscopic Transnasal Transsphenoidal Pituitary Tumor Resection.

Background: Dexmedetomidine is associated with good perioperative hemodynamics together with decreased opioid requirements. Furthermore, propofol has been used to achieve hypotensive anesthesia as a part of total intravenous anesthesia. Aims: This study was performed to compare dexmedetomidine and propofol on the adequacy of hypotensive anesthesia during transsphenoidal resection of pituitary tumors. Patients and
Methods: A total of 110 cases were included in this prospective randomized study. They were randomized into two equal groups; Group D commenced on Dexmedetomidine, and Group P, which received propofol. Comparing intraoperative hemodynamic parameters and the Boezaart Bleeding Scale was our primary outcome. The secondary outcomes included isoflurane and propranolol consumption, recovery, postoperative analgesic profile. Statistical Analysis: IBM's SPSS Statistics (Statistical Package for the Social Sciences) for Windows (version 25, 2017) was used for the statistical analysis of the collected data. Shapiro-Wilk test was used to check the normality of the data distribution. The quantitative variables were expressed as mean and standard deviation, whereas the categorical variables were expressed as frequency and percentage. Independent sample t and Mann - Whitney tests were used for the comparison of parametric and nonparametric continuous data, respectively. For pair-wise comparison of data (within-subjects), the follow-up values were compared to their corresponding basal value using the paired samples t-test or Wilcoxon matched-pairs signed-ranks test. Fisher exact and Chi-square tests were used for inter-group comparison of nominal data using the crosstabs function.
Results: Age, gender, body mass index, and systemic comorbidities did not significantly differ between the two groups. Furthermore, heart rate and blood pressure were comparable at baseline, during operation, and after extubation. Boezaart score, blood loss, isoflurane, and propranolol consumption were also comparable between the two groups. Group D expressed significantly longer emergence and extubation times than Group P. Nevertheless, cases in the same group expressed lower Visual Analog Scale values and postoperative analgesic requirements.
Conclusion: Although Dexmedetomidine and propofol are associated with comparable intraoperative hemodynamic changes, the former drug appears to be superior regarding pain control, postoperative analgesic requirement. Copyright:

INTRODUCTION

Neuroanesthesia has some basic principles, including smooth induction, hemodynamic stability, maintaining cerebral perfusion and providing optimal operative conditions to facilitate good exposure for the surgeon. Smooth emergence is also as important as smooth induction as it allows the early assessment of the neurological functions after surgery.[1]

Transsphenoidal resection of pituitary tumors is a common neurosurgical procedure, as it accounts for 20% of all intracranial operations in most neurosurgical centers.[2] Anesthetic management for such cases represents a challenge to anesthesiologists as nasal speculum insertion during the procedure results in a strong nociceptive stimulation, leading to tachycardia and hypertension. This will lead to bleeding and difficult visualization of the operative field.[34]

Multiple drugs have been recommended to achieve controlled hypotension during neurosurgical procedures, including beta-blockers, sodium nitroprusside, nitroglycerine, increasing the doses of inhaled anesthetics, alpha-2 agonists, and magnesium sulfate.[567]

Propofol, a widely used intravenous anesthetic agent, has been used to achieve hypotensive anesthesia due to its potent hypotensive action. Its short-term infusion is safe, and normal blood pressure is rapidly restored after its discontinuation.[8]

Dexmedetomidine is a selective alpha-2 adrenergic receptor agonist that has sedative, analgesic, and anesthetic sparing effects without any negative impact on the respiratory center. It modulates pain signals transmission through acting on both spinal and supraspinal regions.[1] It is also associated with decrease inhaled anesthetic requirements.[9] In addition, in neurosurgical patients, it helps to stabilize intracranial pressure along with intraoperative hemodynamic stability, especially on intubation and extubation. It also allows earlier awakening due to decreased anesthetic and opioid consumption.[1011]

According to our knowledge, there is a paucity of studies comparing the effects of dexmedetomidine and propofol on the adequacy of hypotensive anesthesia during transsphenoidal resection of pituitary tumors. Thus, we conducted the current study aiming to compare these two drugs on the adequacy of hypotensive anesthesia during transsphenoidal resection of pituitary tumors.

PATIENTS AND METHODS

This is a prospective randomized study that was conducted at Mansoura University hospitals during the period of 2 years, starting from December 2019 to December 2021. The study was designed for adult cases aged between 18 and 65 years who were electively prepared for pituitary tumor resection. On the other hand, patients with Glasgow Coma Scale <15, American Society of Anesthesiologists physical status class score >II, preoperative hear rate <50 bpm, first- or second-degree heart block, allergy to the study medications, and pregnancy were excluded. In addition, patients commenced on beta-blockers, alpha-methyl dopa, clonidine, or other alpha-2 agonists were excluded.

The sample size was computed based on a previous study,[12] where at the time of nasal speculum insertion, the increase in mean arterial pressure (MAP) was 9.4% in the Dexmedetomidine group, on G power to detect a difference of 20% in MAP between the propofol group and the dexmedetomidine group. The required sample size for α error of 0.05 and power of 80% was estimated to be 55 patients per group.

Before surgery, informed written consent was obtained from all of the participants after a detailed explanation of the details of the surgical procedure, pros and cons of each medication. Furthermore, the study gained approval from the Institutional Review Board of the faculty of medicine, Mansoura University with reference number R.21.09.1454 at November 20, 2021.

The included 110 cases were randomly allocated using a computer-generated randomization table into two equal groups; Group D, which included 55 cases which were commenced on dexmedetomidine (1 mcg. kg−1 over 10 min followed by a maintenance of 0.5 mcg. kg−1.h−1), and Group P which included the remaining 55 cases who received propofol (150 μg.kg−1.h−1 initially which was titrated to maintain MAP between 55 and 65 mmHg with stable hemodynamics). Both drugs were prepared by a staff nurse in an opaque syringe and an anesthesiologist who were blind to both drug and patient allocation.

On arrival at the neurosurgical operative theater, the standard patient monitoring was ensured, including noninvasive arterial pressure, pulse and oxygen saturation. In addition, an intravenous line was established. Before induction, midazolam (0.03 mg.kg−1) was given in all cases. Induction of anesthesia was done by propofol (0.5–2 mg.kg−1), whereas atracurium (0.5 mg.kg−1) was used for neuromuscular blockade. Then, direct laryngoscopy with insertion of the appropriate size endotracheal tube was done.

Anesthesia was maintained with air in oxygen (50%:50%) and isoflurane. Intermittent positive pressure ventilation with a tidal volume of 7–8 mL. kg body weight was done to maintain end-tidal carbon dioxide between 30 and 35 mm Hg. Furthermore, a moist cotton gauze was used to pack the posterior pharynx under direct laryngoscopy.

If any rise in the heart rate or mean blood pressure >20%, compared to the baseline, the initial isoflurane 0.5% end-tidal concentration was increased by 0.2% every 4 min up to a maximum of 2% end-tidal concentration. If no response was detected, either nitroglycerine (increment 0.1–0.25 mg) or propranolol (increment 0.5 up to 2 mg) was administered.

Both blood pressure and pulse were measured and monitored. It has been recorded at the following time points; baseline, before intubation, after intubation, insertion of a nasal speculum, at 15 min, 30 min, then after 30 min till the end of the surgery, preextubation, and postextubation.

Suppose hypotension was detected, defined as systolic blood pressure <90 mmHg, ephedrine 5 mg was given intravenously. Besides, bradycardia, defined as heart rate <50 bpm, was managed by intravenous atropine (0.02 mg.kg−1).

Boezaart Bleeding Scale was used to evaluate the quality of surgical field regarding blood loss as follows; (0) virtually bloodless field, (1) slight oozing for which suctioning is not essential, (2) mild bleeding requiring occasional suctioning without interference with the surgical field, (3) moderate bleeding requiring usual suctioning that improves the visual field, (4) heavy bleeding with frequent suctioning, and the surgical field worsens after suction is removed, (5) severe uncontrollable bleeding faster than suctioning.[13]

Blood loss, fluid intake, and urine output were measured and recorded. Both propofol and dexmedetomidine were discontinued 10 min before the end of the surgery, which was defined as the time point when the neurosurgeon removed the nasal speculum. After that, isoflurane was ceased, and neuromuscular blockade was reversed by neostigmine and atropine. The total doses of isoflurane, propranolol, and nitroglycerine were calculated and recorded. The total isoflurane dose was calculated as recommended by Biro.[14]

In addition, both emergence and extubation times were recorded. Emergence time was defined as the time interval between isoflurane discontinuation and time to spontaneous eye opening in response to a verbal command.[15] Extubation time was defined as the time interval between isoflurane and extubation.[16]

All patients were then moved to the neurosurgery intensive care unit (ICU), where observation was continued by an investigator and an ICU nurse, neither of whom was aware of the anesthetic regimen. Postoperative pain was evaluated by the Visual Analog Scale (VAS), with 0 for no pain and 10 for the worst pain ever.[17]

Comparing intraoperative hemodynamic parameters along with the Boezaart Bleeding Scale were our primary outcomes. The secondary outcomes included inhalational anesthetic requirement, hypotensive agent doses required, emergence time, extubation time, postoperative pain, and analgesic requirements.

Statistical analysis

IBM's Statistical Package for the Social Sciences (SPSS) statistics for Windows (version 25, 2017) (IBM corporation, Armonk, NY, USA) was used for the statistical analysis of the collected data. Shapiro–Wilk test was used to check the normality of the data distribution. Quantitative variables were expressed as mean and standard deviation, whereas categorical variables were expressed as frequency and percentage. Independent sample T and Mann − Whitney tests were used for the comparison of parametric and nonparametric continuous data, respectively. For pair-wise comparison of data (within-subjects), the follow-up values were compared to their corresponding basal value using the paired samples t-test or Wilcoxon matched-pairs signed-ranks test. Fisher exact and Chi-square tests were used for inter-group comparison of nominal data using the crosstabs function.

RESULTS

Both age and gender were not significantly different between the two groups (P = 0.640 and 0.565 respectively). The mean age of the included cases was 46.62 and 45.75 years in groups D and P, respectively. Males represented 58.2 and 52.7% of the included population in both groups, respectively. In addition, the mean values of body mass index were 30.1 and 29.77 kg.m2 in the study groups, respectively (P = 0.693). Diabetes mellitus was present in 3.6% and 9.1% of cases, whereas hypertension was prevalent in 20% and 18.2% of cases in the same groups, respectively. Operative time did not significantly differ between the study groups (160.91 and 153 min, respectively, – P = 0.155). Table 1 illustrates these data.

Table 1

Demographic characteristics, medical history and operative duration of the study groups

	Group D (n=55)	Group P (n=55)	95% CI	P
Age (years)	46.62±8.272	45.75±11.029	−2.8-4.6	0.640
Gender, n (%)
Male	32 (58.2)	29 (52.7)		0.565
Female	23 (41.8)	26 (47.3)
BMI (kg/m2)	30.10±4.408	29.77±4.378	−1.3-2.0	0.693
History of DM, n (%)	2 (3.6)	5 (9.1)		0.438
History of HTN, n (%)	11 (20.0)	10 (18.2)		0.808
Operative duration (min)	160.91±29.644	153.00±28.196	−3.0-18.8	0.155

CI=Confidence interval, BMI=Body mass index, DM=Diabetes mellitus, HTN=Hypertension

Basal, intraoperative, and postextubation heart rate measurements were statistically comparable between the two groups (P > 0.05). These data are illustrated in Table 2.

Table 2

Basal and follow-up values of the study groups’ heart rate (beat/min)

Heart rate	Group D (n=55)	Group P (n=55)	95% CI	P
Basal	85.38±7.529	87.02±8.565	−4.7-1.4	0.290
Drug infusion	82.04±7.338	84.75±8.438	−5.7-0.3	0.075
Before intubation	69.76±7.608	72.62±8.489	−5.9-0.2	0.066
After intubation	63.33±9.862	65.75±8.765	−5.9-1.1	0.177
Speculum insertion	63.07±9.903	65.58±9.028	−6.1-1.1	0.168
15 min	62.96±10.132	65.42±8.908	−6.1-1.2	0.180
30 min	63.20±10.853	64.87±9.111	−5.5-2.1	0.383
60 min	62.91±10.814	65.22±10.208	−6.3-1.7	0.252
90 min	62.67±10.844	64.65±10.442	−6.0-2.0	0.331
120 min	62.61±10.931	65.53±10.724	−7.1-1.3	0.168
150 min	62.83±11.878	65.34±10.190	−7.8-2.7	0.343
180 min	62.80±14.088	66.00±9.390	−12.3-5.9	0.477
210 min	65.00±9.899	68.67±1.528	−20.7-13.3	0.542
Preextubation	71.91±11.546	64.76±10.770	−5.1-3.4	0.689
Postextubation	71.91±11.699	66.80±11.697	−7.3-1.5	0.198

CI=Confidence interval

Mean arterial blood pressure values did not significantly differ between the two groups at baseline or during drug infusion. Table 3 illustrates these data.

Table 3

Basal and follow-up values of mean arterial pressure (mmHg) of the study groups

MAP	Group D (n=55)	Group P (n=55)	95% CI	P
Basal	98.18±4.750	97.07±4.086	−0.6-2.8	0.192
Drug infusion	94.27±5.523	95.96±4.872	−3.7-0.3	0.091
Before intubation	59.29±7.099	58.93±5.878	−2.1-2.8	0.770
After intubation	62.27±8.031	61.71±7.305	−2.3-3.5	0.701
Speculum insertion	62.85±7.663	61.75±7.594	−1.8-4.0	0.447
15 min	62.78±7.932	62.20±7.936	−2.4-3.6	0.701
30 min	62.91±8.307	62.09±8.336	−2.3-4.0	0.607
60 min	62.96±8.583	61.75±8.596	−2.0-4.5	0.459
90 min	62.85±8.864	61.67±8.428	−2.1-4.5	0.475
120 min	62.86±8.591	62.07±8.813	−2.6-4.1	0.642
150 min	62.93±8.658	61.25±6.979	−2.1-5.4	0.375
180 min	64.40±7.500	59.85±5.352	−0.4-9.5	0.068
210 min	65.00±0.0	64.33±4.041	−8.9-10.3	0.839
Preextubation	77.82±9.145	77.18±7.818	−2.6-3.9	0.696
Postextubation	81.93±10.274	79.31±9.379	−1.1-6.3	0.166

MAP=Mean arterial pressure, CI=Confidence interval

The mean values of Boezaart score were significantly lower in Group D than Group P (1.43 vs. 1.57 respectively– P = 0.033). In addition, propranolol consumption showed a significant decrease in Group D (P < 0.001). Nevertheless, isoflurane consumption and blood loss showed no significant difference when comparing the same groups. Furthermore, neither intraoperative fluid intake nor urine output was significantly different between the two groups (P = 0.616 and 0.225, respectively).

In addition, Group D expressed significantly longer emergence and extubation times than Group P. However, cases in the same group expressed significantly higher VAS values (P = 0.018) and a higher postoperative analgesic requirement (P = 0.04). Table 4 summarizes these data.

Table 4

Intra-operative isoflurane, propranolol and nitroglycerine consumption, Boezaart score, fluid intake, urine output, blood loss, emergence and extubation times, postoperative Visual Analog Scale score and morphine requirements of the study groups

	Group D (n=55)	Group P (n=55)	95% CI	P
Boezaart	1.43±0.4325	1.57±0.369	−0.3-0.0	0.033
Isoflurane consumption (mL)	51.64±11.509	51.45±15.446	−4.9-5.3	0.944
Propranolol consumption/per patient	0.31±0.245	0.49±0.663	−0.4-0	0.059
Intraoperative fluid intake (mL)	1556.3±376.0	1522.7±322.7	−99-166	0.616
Urine output (mL)	740.91±230.55	692.73±180.12	−30-126	0.225
Blood loss (mL)	230.45±52.19	249.09±62.54	−40-3	0.093
Emergence time (min)	10.27±2.670	7.47±2.176	1.9-3.7	<0.001
Extubation time (min)	13.62±2.812	10.58±2.580	2.0-4.1	<0.001
VAS	2.18±0.75	3.20±0.97	−1.3-−0.7	<0.001
Postoperative morphine requirements	1.02±1.147	1.60±0.955	−1-−0.2	0.005

CI=Confidence interval, VAS=Visual Analog Scale

DISCUSSION

As earlier clinical investigations have pointed to the efficacy of Dexmedetomidine as a sedative in critically ill patients, newer studies have focused on the efficacy of alpha-2 receptor agonists as adjuvants to neuroanesthesia. Dexmedetomidine has multiple favorable clinical effects, including hemodynamic stability, neuroprotection, lack of respiratory depression without interference with intraoperative neurophysiological monitoring. These pros suggest that dexmedetomidine could be useful in the management of neurosurgical patients.[18]

The current study was conducted at Mansoura University Hospitals, aiming to compare Dexmedetomidine and propofol on the adequacy of hypotensive anesthesia during transsphenoidal resection of pituitary tumors. A total of 110 cases was included, and they were divided into two groups; Group D (55 cases), which was commenced on Dexmedetomidine, and Group P (55 cases), which received Propofol.

No significant differences were detected between the two study groups as regard demographic characteristics, and that should nullify any bias that may have skewed results in favor of one group rather than the other one. Moshiri et al. also conducted a study in 2017, which handled the same perspective as ours, but in endoscopic sinus surgeries, reported no significant difference between the two groups regarding most of the preoperative data,[19] which confirms our findings.

In the current study, both groups expressed comparable heart rate and blood pressure findings at baseline, during operation or after extubation. Similarly, Godbole et al., reported almost no significant difference between propofol and Dexmedetomidine regarding heart rate or blood pressure. Their study compared the same pharmacological agents regarding maintaining hypotensive anesthesia during ENT surgeries.[20] Another study stated that both drugs were successful in maintaining hypotension. However, more reduction of heart rate was encountered in the propofol group.[19]

Cardiovascular response in the form of tachycardia and hypertension is frequently encountered in multiple intracranial surgical procedures. About 50%–90% of such cases require perioperative antihypertensive agents to control blood pressure.[2122] Due to severe nociceptive stimuli experienced by the patients during transsphenoidal pituitary surgeries, the anesthesiologist often encounters perturbations in heart rate and blood pressure during multiple surgical stages. This will require increasing the depth of anesthesia or increasing opioid administration, leading to hypotension with a compromise of the cerebral circulation. Besides, these maneuvers are associated with prolonged recovery time.[2324]

In intragroup comparison, one should notice the significant decrease in the MAP and heart rates during operation compared to the baseline. In line with our findings, Bala et al. reported that dexmedetomidine administration was associated with a significant decrease in mean arterial blood pressure and heart rate compared to controls despite being comparable at baseline.[12] Batra et al. also reported that both heart rate and blood pressure readings had lower values in the dexmedetomidine group than controls throughout most intraoperative readings. However, both groups had no significant difference before operation.[1] Moreover, other studies have confirmed our findings regarding the effectiveness of dexmedetomidine in maintaining hemodynamic stability in pituitary surgeries.[2325]

Multiple previous studies have confirmed the efficacy of dexmedetomidine in attenuating the changes in intraoperative hemodynamics. Therefore, it gained great popularity in neurosurgical procedures.[262728] Its central and peripheral actions could explain these effects. In the central nervous system, it decreases the sympathetic outflow. In addition, it blocks peripheral ganglia. The previous mechanisms could explain its protective effect on hemodynamic changes during neurosurgical procedures.[12]

The previous reports emphasize the importance of dexmedetomidine as adjunctive to general anesthesia in such cases, as it decreases the occurrence of hypertensive episodes, which can lead to bleeding, edema, worsened surgical field, and increased intracranial pressure.[22]

When it comes to propofol and its effects on hemodynamics in the current study, it had similar effects to dexmedetomidine. Propofol is also known to induce bradycardia in humans due to sympathetic inhibition.[29] It also induces hypotension through decreasing cardiac output and systemic vascular resistance. This drug has a unique advantage; when the heart rate increases due to blood pressure decrease, it is decreased through suppression of the baroreceptor reflex.[30] The previous facts are in line with our findings.

In the current study, the mean values of the Boezaart score were comparable between the two groups. These effects are secondary to better hypotensive anesthesia with both agents, leading to decreased tissue oozing during surgical dissection, especially in narrow surgical fields like those encountered in neurosurgical practice.

Multiple studies have documented that better surgical field visibility is directly related to hypotensive anesthesia and heart rate.[3132] As both agents had comparable heart rates and MAP during operation, we expected to find comparable results regarding surgical field quality. This was also evident in our study's blood loss, which was comparable between the two groups.

Similar to our findings, Moshiri et al. et al. reported no significant difference between the two groups regarding bleeding score (P = 0.490), which had mean values of 1.14 and 1.24 in the Dexmedetomidine and propofol groups, respectively.[19]

Moreover, other authors confirmed the efficacy of propofol infusion in improving the quality of the surgical field through deliberate hypotension. However, this study was conducted on patients undergoing endoscopic sinus surgery.[33]

In our study, Group D had comparable isoflurane consumption between the two study groups. Dexmedetomidine is associated with decreased inhalation anesthetic requirement because of its α-2 agonist actions, which inhibit noradrenergic transmission.[3435] Its sedative effect is associated with a 35%–50% reduction in intraoperative isoflurane requirements.[36] This was documented in three previous studies that reported that dexmedetomidine administration led to decreased inhalation anesthetic intake.[123738] Of course, this will lead to a faster and better recovery from anesthesia, allowing early assessment of the patient's neurological functions after the operation.

In the current study, propranolol administration was comparable between the two study groups. This is secondary to the obtained heart rate and blood pressure measurements during surgery. It was comparable between the two groups, which led to a more or less similar propranolol dose between the two groups.

Our findings revealed that Group P expressed significantly shorter emergence and extubation times than Group D. Both early emergence and tracheal extubation are crucial for neurosurgical anesthesia. Similarly, Gunes et al. noted delayed recovery after intracranial surgery in patients administered dexmedetomidine.[39]

Moshiri et al. reported comparable recovery time between both agents (P = 0.166), which had mean values of 32.52 and 29.9 min in the dexmedetomidine and propofol groups, respectively.[19]

On the contrary, Tanskanen et al. and Ilhan et al. also noted that the dexmedetomidine infusion was associated with faster recovery from general anesthesia. They also reported no cases with respiratory depression that may delay patient recovery.[2240]

When it comes to postoperative pain, Group D expressed significantly lower VAS values and lower postoperative analgesic requirements. In the same context, a previous study has reported that the analgesic effects of dexmedetomidine are not negligible, as it was associated with a significant decrease in the perioperative opioid consumption in cases undergoing minor surgeries.[36] This analgesic effect is mediated through alpha-2 receptors located at the spinal cord and the supraspinal and peripheral sites.[41] This, in turn, will impact postoperative analgesic consumption, which showed a significant decrease in the same group.

All in all, one should notice the comparable intraoperative effects of both drugs. Dexmedetomidine had the upper hand on the postoperative analgesic profile, while propofol showed its superiority in the recovery profile. Another point that should be considered is that propofol needs frequent change in the rate of infusion according to blood pressure measurements, which was needed in the other group. This added another advantage to the dexmedetomidine.

Our study has multiple limitations; first, it is a single center study that included a relatively small sample size. Furthermore, the efficacy of dexmedetomidine in patients with preexisting heart disease should have been studied. In addition, stress hormone levels (like cortisol) should have been evaluated as well. These drawbacks should be well covered in the upcoming studies.

CONCLUSION

Based on our findings, although dexmedetomidine and propofol are associated with comparable intraoperative hemodynamic changes and blood loss, the former drug appears to be superior regarding pain control, postoperative analgesic requirement.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.