Ultrasonographic measurement of optic nerve sheath diameter (ONSD) can be used to monitor intracranial pressure (ICP), as it closely corresponds with assessments of ICP made using invasive methods [1]. While the impact of robotic-assisted surgery on ONSD has been explored, limited research is available on the effects of robotic-assisted kidney transplant (RAKT) on ONSD in patients with end-stage renal disease [1]. Patients with chronic kidney disease (CKD) present differently from the populations previously studied, as end-stage renal disease can produce changes in the cerebral vasculature and increase the risk of spontaneous subdural hemorrhage, disequilibrium syndrome, various forms of encephalopathy, and cognitive impairment [2]. Individuals receiving hemodialysis can experience interstitial cerebral edema, which may be exacerbated by urea [3]. Consequently, application of the steep Trendelenburg (ST) position and pneumoperitoneum may exert a greater impact on these individuals compared to others. Additionally, these patients often display chronic hypertension and volume overload. Chronic hypertension can elevate cerebral vascular resistance and predispose individuals to cerebral ischemia.

Mean arterial pressure (MAP) has previously been associated with changes in ONSD [1]. During renal transplantation, MAP is intentionally elevated leading up to reperfusion to ensure adequate graft perfusion and promote early graft function, achieved by administering intravenous fluids and vasopressors as needed [4]. This elevation may also impact ONSD. Additionally, the administration of furosemide and mannitol during reperfusion, as well as the open ureteric anastomosis and the release of pneumoperitoneum, can influence ONSD and ICP. Therefore, we investigated the effect of RAKT on ONSD/ICP in this high-risk group.

The primary objective of this study was to evaluate changes in ONSD as an indirect indicator of ICP fluctuations at various intervals throughout RAKT. This research was conducted on adults undergoing RAKT at our institution over a 1-year period. A secondary aim was to explore the potential correlations between perioperative hemodynamic parameters and changes in ONSD.

The study received approval from the Institutional Research and Ethics Committee of Aster Medcity, Kochi (approval no. AM/EC/97-2019) and was registered with the Clinical Trial Registry - India (ICMR-NIMS) under the identifier CTRI2020/09/027930. The research adhered to the ethical principles outlined in the Declaration of Helsinki. All participants provided informed consent prior to their inclusion in the study.

This prospective observational study was conducted at our institution and included 20 adult patients ranging in age from 18 to 60 years. These patients underwent live-donor RAKT between September 2020 and September 2021.

The primary aim of the study was to evaluate changes in ONSD as an indirect indicator of ICP fluctuations during RAKT at several time points: T1, shortly after intubation; T2, after assuming the ST position; T3, 1 hour postdocking; T4, immediately after reperfusion; T5, upon transition to the supine position; and T6, 3 hours after extubation. The secondary objective was to identify any associations between changes in ONSD and fluctuations in heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), MAP, or central venous pressure (CVP). Patients who declined to give consent were excluded from the study. Those with a history of neurological diseases, transient ischemic attacks, carotid disease, intracranial diseases, glaucoma, or prior ocular surgery were also excluded.

Patients were administered ondansetron (4 mg), pantoprazole (40 mg), alprazolam (0.25 mg), and antihypertensive medications on the evening before and the morning of surgery. The immunosuppression regimen for recipients included mycophenolate mofetil (35 mg/kg) and tacrolimus (0.1 mg/kg), initiated 2 days before surgery. An additional dose of basiliximab (20 mg) was given to recipients with donors who were not first-degree relatives. During the operation, patients received an intraoperative dose of methylprednisolone (7.5 mg/kg) prior to kidney placement. All recipients underwent hemodialysis 24 hours before the transplant.

In addition to standard monitoring, we utilized an arterial line, a central venous triple lumen catheter, and a bispectral index monitor for all patients. Induction of anesthesia was achieved using midazolam (0.02–0.04 mg/kg), fentanyl (3–4 μg/kg), propofol (1–2 mg/kg), and atracurium (0.5 mg/kg). Anesthesia was maintained with a mixture of air and oxygen, desflurane, and continuous infusions of atracurium (0.5 mg/kg/hr) and dexmedetomidine (0.2–0.5 μg/kg/hr). Following tracheal intubation, patients were placed on volume-controlled mechanical ventilation. We used a tidal volume of 6–8 mL/kg of ideal body weight and adjusted the respiratory rate to achieve normocarbia (30–35 mmHg). The inspiratory-to-expiratory time ratio was set at 1:2, with positive end-expiratory pressure maintained at 5 mmHg. Peak inspiratory pressure was limited to 35 mmHg.

Until kidney implantation, all patients were managed with a restrictive fluid strategy, utilizing crystalloids at a rate of 1 mL/kg/hr. This was subsequently replaced by a more liberal fluid regimen (1.50–1.75 mL/kg/hr). Additionally, we administered furosemide (1.5–2.0 mg/kg) to induce diuresis. Prior to reperfusion, mannitol was also administered at a dose of 0.25 to 0.5 g/kg.

To protect them from injury, the eyes were closed with transparent adherent dressings after the application of methylcellulose eye ointment. We used a high-frequency linear probe with a frequency of 6–13 Hz and a 38-mm footprint (Sonosite M-Turbo ultrasound system; FUJIFILM Sonosite), operating at reduced acoustic power. The probe, coated with gel, was placed gently to avoid injuring the retina and lens. The ultrasound beam was adjusted to obtain a suitable angle for visualizing the entry of the optic nerve into the globe, enabling the measurement of ONSD. Two senior anesthetists, each with 10 years of experience in ultrasonography, performed the measurements to minimize observational bias, and the average of their readings was recorded. The ONSD was measured 3 mm behind the optic disc (Fig. 1). Measurements were taken of the ONSD of both eyes, along with HR, SBP, DBP, MAP, and CVP. For the analyses, we used the mean of two values from each eye.

Figure 1. Ultrasonographic measurement of the optic nerve sheath diameter (ONSD). The ONSD (B) was measured 3 mm behind the optic nerve (A).

The following patient characteristics were recorded: age, body mass index, diagnosis, comorbidities, and preoperative dialysis and fluid removal, as well as preoperative levels of sodium, blood glucose, hemoglobin, and creatinine. Additionally, postoperative levels of sodium and glucose were measured prior to extubation. Also documented were the duration of surgery and anesthesia, the time spent in the ST position with pneumoperitoneum, the total volume of intraoperative fluids administered, and any perioperative complications, along with the dosage of furosemide administered, the intraoperative urine output, the time required for extubation, and the recovery and emergence times.

A single surgeon, proficient with Da Vinci systems (Intuitive Surgical), operated on all recipients. The patient was placed in the lithotomy position, and pneumoperitoneum was established by the insufflation of carbon dioxide (CO₂) through a Veress needle. The patient was then tilted to a 30°–45° Trendelenburg position, and the robot was docked. The intra-abdominal pressure was initially kept below 15 mmHg. Following reperfusion of the transplanted kidney, the pneumoperitoneum was fully released, and the ureteric anastomosis was completed via the gel port that had been used for kidney insertion. On-table extubation was attempted for all patients. After surgery, patients were transferred to the intensive care unit, where the final measurements of ONSD and other parameters were taken 3 hours after extubation. For 24 hours after the transplant, we monitored and documented any behavioral changes, altered levels of consciousness, headache, lethargy, and neurological symptoms, such as weakness, numbness, issues with eye movement, double vision, seizures, drowsiness, ocular palsy, nausea, and vomiting.

Statistical Analysis

Statistical analysis was performed using IBM SPSS ver. 22 (IBM Corp.). Data were expressed using descriptive statistics, including mean±standard deviation, median (range), or frequency and percentage. The Kolmogorov-Smirnov test was used to assess the normality of data distribution. Repeated measures analysis of variance (ANOVA) with post hoc Bonferroni correction was employed to compare ONSD, MAP, DBP SBP, HR, and CVP at the various time points. Pearson correlation analysis was utilized to investigate the relationships between ONSD and the hemodynamic and perioperative variables. P-values of 0.05 or less were considered to indicate statistical significance.

Between September 2020 and September 2021, 26 patients underwent RAKT. Of these, three were pediatric patients, and another three patients declined to provide consent. Thus, our study included 20 patients, all of whom were male and scheduled for RAKT. Accordingly, we measured the ONSD of 40 eyes. No significant differences in demographic or clinical characteristics were observed among the patients. Baseline demographics, comorbidities, and perioperative clinical variables are summarized in Table 1 and Fig. 2. All patients were classified as American Society of Anesthesiologists category III. The assumption of the ST position and the establishment of CO₂ pneumoperitoneum were associated with a significant initial increase in ONSD (Table 2, Fig. 3). The ONSD was highest at T3 (mean ONSD, 3.6023 to 4.0637 mm). The maximum ONSD recorded in a patient was 5.05 mm at T3. Three patients exhibited an ONSD greater than 4.8 mm, suggesting an ICP greater than 20 mmHg. Repeated measures ANOVA indicated that the mean ONSD differed statistically significantly between time points. Post hoc tests with the Bonferroni correction showed that ONSD increased from T1 (3.60±0.44) to T3 (4.06±0.45, P=0.002) and from T1 to T4 (3.99±0.62, P=0.046). Subsequently, ONSD decreased from T3 (4.06±0.45) to T5 (3.54±0.47) and from T3 to T6 (3.42±0.64), which represented significant changes (P=0.002 for both) (Table 2). No intraoperative complications were reported. Additionally, no ocular or neurological complications were clinically observed 24 hours after extubation.

Table 1. Demographic, preoperative, and postoperative variables

Variable	Value
Demographic
Age (yr)	43.15±12.22
Height (cm)	163.42±10.15
Body mass index (kg/m2)	23.29±3.80
Preoperative
Total fluid removed (hemodialysis; mL)	1,552±578
Sodium (meq/L)	134.62±6.53
Fasting blood glucose (mg/dL)	120.80±22.90
Hemoglobin (gm/dL)	11.41±1.78
Duration of surgery (min)	262.00±53.58
Creatinine (mg/dL)	5.645±1.900
Duration of anesthesia (min)	345.55±50.52
Duration of Trendelenburg position (min)	201.60±47.93
Intraoperative fluid administered (mL)	3,045±1,004
Postoperative
Sodium (meq/L)	134.29±4.69
Glucose before extubation (mg/dL)	175.20±43.72
Furosemide dosage (mg)	96.50±16.31
Intraoperative urine output (mL)	1,060±438
Tracheal extubation time (min)a)	10.05±3.98
Recovery time (min)b)	13.70±8.19
Emergence time (min)c)	9.85±5.96

Values are presented as mean±standard deviation.

^a)Tracheal extubation time denotes the interval from discontinuation of anesthesia to tracheal extubation; ^b)Time elapsed from discontinuation of anesthesia to the point when the patient could recall their name and date of birth; ^c)Duration from drug discontinuation to the time the patient opened their eyes.

Table 2. Comparisons between ONSD, SBP, DBP, and MAP at predetermined time points

Variable	Mean±SD	P-valuea)	P-valueb) for mean difference between points
			T1	T2	T3	T4	T5
ONSD (mm)		<0.001
T1	3.60±0.44		-	-	-	-	-
T2	3.99±0.61		0.067	-	-	-	-
T3	4.06±0.45		0.002	>0.999	-	-	-
T4	3.99±0.62		0.046	>0.999	>0.999	-	-
T5	3.54±0.47		>0.999	0.083	0.002	0.047	-
T6	3.42±0.64		>0.999	0.076	0.002	0.063	>0.999
SBP (mmHg)		<0.001
T1	130.50±23.88		-	-	-	-	-
T2	158.40±32.60		0.004	-	-	-	-
T3	143.60±20.27		0.347	0.849	-	-	-
T4	152.95±16.10		0.004	>0.999	0.817	-	-
T5	146.35±18.35		0.331	>0.999	>0.999	>0.999	-
T6	167.45±25.84		<0.001	>0.999	0.033	0.107	0.017
DBP (mmHg)		<0.001
T1	75.45±13.47		-	-	-	-	-
T2	100.70±24.78		0.001	-	-	-	-
T3	91.85±14.49		<0.001	>0.999	-	-	-
T4	88.20±16.41		0.023	0.414	>0.999	-	-
T5	83.45±13.22		0.541	0.083	0.147	>0.999	-
T6	87.80±16.52		0.009	0.168	>0.999	>0.999	>0.999
MAP (mmHg)		<0.001
T1	93.95±17.71		-	-	-	-	-
T2	120.65±26.22		0.002	-	-	-	-
T3	111.15±16.98		0.009	>0.999	-	-	-
T4	107.30±28.03		0.587	0.746	>0.999	-	-
T5	103.75±14.32		0.587	0.106	>0.999	>0.999	-
T6	117.00±18.02		<0.001	>0.999	>0.999	>0.999	0.054

ONSD, optic nerve sheath diameter; SBP, systolic blood pressure; DBP, diastolic blood pressure; MAP, mean arterial pressure; SD, standard deviation; T1, 10 minutes after intubation; T2, upon assuming the steep Trendelenburg position after docking; T3, 1 hour postdocking; T4, upon reperfusion; T5, after transition to the supine position; T6, 3 hours postextubation.

^a)Repeated measures analysis of variance; ^b)Post hoc Bonferroni correction.

P<0.05 indicates statistical significance.

Figure 2. Associated comorbidities. 0, no comorbidities; 1, hypertension; 2, diabetes; 3, coronary arterial disease; 4, dyslipidemia; 5, moderate pulmonary artery hypertension; 6, smoking; 7, hepatitis C; 8, valvular heart disease.

Figure 3. Optic nerve sheath diameter (ONSD) variation at predetermined time points. T1, 10 minutes after intubation; T2, upon assuming the steep Trendelenburg position after docking; T3, 1 hour postdocking; T4, upon reperfusion; T5, after transition to the supine position; T6, 3 hours postextubation.

We observed significant increases in SBP between T1 and T2 (P=0.004), between T1 and T4 (P=0.004), and between T1 and T6 (P<0.001) (Table 2, Fig. 4). DBP also exhibited significant increases from the T1 measurement to T2 (P=0.001), T3 (P<0.001), T4 (P=0.023), and T6 (P=0.009) (Table 2, Fig. 4). MAP exhibited significant differences between T1 and T2 (P=0.002), T3 (P=0.009), and T6 (P<0.001) (Table 2, Fig. 4). CVP after positioning demonstrated a significant increase between T1 and T3 (P=0.017) and between T1 and T4 (P=0.036). Subsequently, CVP decreased significantly, returning to baseline levels at T6. No significant differences were observed in HR at the various time points. Postoperatively, none of the patients exhibited clinical signs of increased ICP. At T3, Pearson correlation analysis revealed significant correlations between ONSD and DBP (r=0.637), as well as between ONSD and MAP (r=0.522; P<0.05 for both) (Table 3). These findings indicate a relationship between these variables at the specified time points. No significant correlations were found between ONSD and SBP, HR, or CVP.

Table 3. Correlation of changes in ONSD with SBP, DBP, MAP, HR, and CVP at predetermined time points

Variable	T1			T2			T3			T4			T5			T6
	r	P-value		r	P-value		r	P-value		r	P-value		r	P-value		r	P-value
SBP (mmHg)	0.028	0.906		0.321	0.167		0.442	0.051		0.411	0.072		0.037	0.878		0.336	0.148
DBP (mmHg)	0.390	0.089		0.417	0.067		0.637	0.003*		0.351	0.129		0.163	0.491		0.348	0.133
MAP (mmHg)	0.196	0.408		0.352	0.128		0.520	0.018*		0.218	0.355		0.215	0.364		0.380	0.099
HR (beats/min)	–0.097	0.684		−0.053	0.824		0.240	0.308		0.060	0.802		−0.390	0.089		0.161	0.499
CVP (mmHg)	0.047	0.863		0.252	0.299		−0.132	0.602		0.309	0.184		−0.234	0.334		−0.003	0.993

ONSD, optic nerve sheath diameter; SBP, systolic blood pressure; DBP, diastolic blood pressure; MAP, mean arterial pressure; HR, heart rate; T1, 10 minutes after intubation; T2, upon assuming the steep Trendelenburg position after docking; T3, 1 hour postdocking; T4, upon reperfusion; T5, after transition to the supine position; T6, 3 hours postextubation; CVP, central venous pressure.

*P<0.05, statistical significance.

Figure 4. Changes in hemodynamic parameters. HR, heart rate; DBP, diastolic blood pressure; MAP, mean arterial pressure; SBP, systolic blood pressure; T1, 10 minutes after intubation; T2, upon assuming the steep Trendelenburg position after docking; T3, 1 hour postdocking; T4, upon reperfusion; T5, after transition to the supine position; T6, 3 hours postextubation.

Based on a previous study by Rajajee et al. [5], we considered an ONSD of more than 4.8 mm to indicate an ICP of more than 20 mmHg, with a sensitivity of 96% and a specificity of 94%. We observed a statistically significant increase in ONSD until reperfusion. This finding aligns with earlier research on robotic-assisted surgery involving pneumoperitoneum and the ST position [1,6–8].

RAKT in the presence of CKD may pose a relatively high risk of developing increased ICP/ONSD compared to other robotic-assisted laparoscopic procedures [3,9,10]. End-stage kidney disease is associated with increased cerebral blood flow, heightened arterial stiffness, and reduced toxin excretion, which can impair the blood-brain barrier and cerebral autoregulation [10–12]. Interstitial cerebral edema is commonly observed in patients with CKD undergoing hemodialysis [3,9]. A high incidence of neurological complications, involving both central and peripheral nervous systems, has been reported in CKD [11–13]. Given these factors, the risk of exacerbating cerebral edema during RAKT is increased [13].

The use of CO₂ pneumoperitoneum and ST positioning to improve surgical exposure in robotic-assisted laparoscopic surgery may result in elevated ICP, reduced cerebral perfusion pressure, and an elevated risk of postoperative cerebrovascular and ocular complications [14–16]. The maximum ONSD observed in our study was 4.06±0.45 mm, occurring at T3 (1 hour postdocking into surgery). This timing corresponded with the placement of the kidney in the body. Following the introduction of the kidney through the gel point, MAP was raised through fluid loading and the administration of vasopressors [17].

In a retrospective study of 177 donations after circulatory death, Snoeijs et al. [18] observed that a MAP above 93 mmHg was associated with better graft function. Similarly, a separate study involving 149 transplants from deceased and living donors indicated that a MAP below 70 mmHg was linked to delayed graft function [19]. Consequently, it is critical to maintain the MAP at 30% above baseline both during and after anastomosis to ensure adequate graft perfusion. This is in contrast to other robotic-assisted procedures, in which maintaining normotension is typically the objective [20]. Following this rationale, we also aimed to maintain the MAP at 30% above baseline in our patients once after kidney implantation.

In our study, we found a significant positive correlation between ONSD at T3 and both DBP and MAP. Similarly, in a study of 51 patients undergoing robotic-assisted radical prostatectomy (RARP), Blecha et al. [21] observed that intraocular pressure was directly correlated with MAP. Furthermore, Balkan et al. [22] reported a significant positive correlation between ONSD and diastolic arterial pressure in their study of 34 patients undergoing RARP.

T3 refers to the time point 1 hour after docking. At this point, ONSD was at its peak, and it demonstrated correlations with MAP and DBP. At this stage, the patient has received intravenous fluids, and the MAP is elevated via the use of vasopressors and inotropes. Despite maintaining MAP at 30% above baseline levels postreperfusion, we noted a significant decrease in ONSD from T4 (reperfusion) to T5 (transition to the supine position). Three hours after extubation, the ONSD was lower than baseline, although this reduction was not statistically significant. This finding contrasts with most studies, in which ONSD either remained unchanged or increased towards the end of surgery [1,6–8]. Following reperfusion, the pneumoperitoneum was released, and an open ureteric anastomosis was established [17]. These actions facilitated CO₂ washout and reduced the peak and plateau pressures associated with pneumoperitoneum and ST position. The decrease in CO₂ after the release of pneumoperitoneum may have led to a reduction in cerebral blood flow and, consequently, a decrease in ONSD/ICP. These surgical steps, combined with the administration of mannitol and furosemide for renal protection, are likely explanations for the observed decrease in ONSD after reperfusion despite the maintenance of elevated MAP [23]. Mannitol and furosemide likely contributed to this effect by inducing diuresis, improving microcirculation, increasing cerebral oxygenation, and thereby reducing brain edema and ICP/ONSD [24]. Consequently, the correlation with MAP and DBP was observed only at T3.

Whiteley et al. [1] postulated that the observed increases in MAP compensated for any increases in ICP, thereby maintaining cerebral perfusion pressure and regional cerebral oxygen saturation. This compensation could be a reason for the very low incidence of neurological complications following RAKT.

CO₂ retention, airway edema, and delayed awakening due to increased ICP make extubation a risky procedure and can postpone recovery. ONSD has been utilized to guide extubation decisions in patients with obesity [25]. None of our patients experienced delayed recovery from anesthesia, and the mean ONSD measurement before extubation (T5) was 3.54±0.47 mm [26].

However, our study had several limitations. Firstly, we did not directly measure ICP, as this is not feasible in non-neurosurgical patients due to the risks of bleeding and infection, as well as ethical concerns. Additionally, our study was limited by its small sample size of only 20 patients. Further research is needed to quantify changes in ONSD when ureteric anastomosis is performed with robotic assistance under pneumoperitoneum. We chose not to measure preinduction ONSD to avoid causing additional discomfort to patients who were already anxious. In all cases, we observed immediate kidney function. It remains uncertain how ONSD trends would differ in cases of delayed graft function. Finally, during the study period, only male patients received transplants. In developing countries, the rate of transplantation in men is significantly higher than in women, which may explain this discrepancy [27].

Although randomized controlled trials are necessary to compare the changes in ONSD between patients with CKD and those without the disease, our findings suggest that ONSD changes in these two demographics are similar until the point of reperfusion. In RAKT, the manipulation of hemodynamics, the use of diuretics, and fluid management distinguish it from other robotic surgical procedures [17]. In their study, Whiteley et al. [1] noted that the highest ICP is likely to occur in the Trendelenburg position at the end of robotic-assisted laparoscopic surgery in patients who do not have CKD. In our study, a decrease in ONSD was observed after T4.

In our study, we excluded patients with significant neurological problems. Three patients exhibited an ONSD corresponding to an ICP greater than 20 mmHg. Therefore, in patients with neurological issues, it is advisable to counsel both the patient and their relatives prior to surgery. We also recommend monitoring ONSD in these individuals, as this can be done with a straightforward, bedside assessment.

Renal transplant recipients undergoing hemodialysis are at high risk of cerebral edema. Concerns may arise about increased ICP within this patient subgroup. Our study demonstrated that RAKT in patients with CKD is associated with elevated ONSD, suggesting a rise in ICP that persists until reperfusion, after which ONSD decreases. Notably, the increase in ONSD was not associated with any neurological complications in patients without a history of neurological disease. Consequently, the rise in ICP attributed to pneumoperitoneum and ST does not pose a problem for these patients. The lowest ONSD value was recorded at 3 hours postextubation. ONSD fluctuations correlate with changes in DBP and MAP up to the point of reperfusion.

Conflict of Interest

No potential conflict of interest relevant to this article was reported.

Author Contributions

Conceptualization: NR, JT. Data Curation: all authors. Formal analysis: NR, JT, SO. Visualization: NR, JT, SO. Writing–original draft: NR, SO. Writing–review & editing: all authors. All authors read and approved the final approved the final manuscript.

Additional Contributions

Dr. Suresh G Nair (Department of Anesthesia and Critical Care, Aster Medcity, India) provided general supervision and contributed to the technical editing of the manuscript. Mr. Abish Sudhakar (Amrita Institute of Medical Sciences and Research Centre, India) offered statistical support and analysis.

Additional Information

This study was presented as an abstract presentation at the Euroanaesthesia 2022 in Milan, Italy, June 4–6, 2022.