Assessment of Optic Nerve Sheath Diameter in Patients... : Nigerian Journal of Clinical Practice (2024)

INTRODUCTION

Elevation of intraluminal and intra-abdominal pressure due to the insufflation of air into the bowel lumen for adequate visualization of the gastrointestinal tract and safe advancement of the endoscope has a variety of physiological and clinical consequences. Impairment of visceral and renal perfusion by increased systemic vascular resistance and venous pressure, deterioration of ventilation, and elevation in intracranial pressure are the main physiologic consequences of elevated intra-abdominal pressure.^[1-4] Besides insufflation, frequently observed conditions such as insufficient sedation, prone or semi-prone patient position, and coughing during the endoscopic retrograde cholangiopancreatography (ERCP) procedure may also increase the intracranial pressure, especially at the time of sphincterotomy.^[2]

Although there are experimental animal studies on intracranial pressure elevation in endoscopic and colonoscopy procedures, to our knowledge, there is no clinical study in the literature that investigates intracranial pressure in ERCP procedures.^[3,5] There is also no evidence in the literature regarding the effect of commonly used sedation agents on changes in intracranial pressure during ERCP. Many studies have shown that propofol reduces ICP.^[6-8] Uncertainty remains due to controversial data concerning the effect of ketamine and ketofol on ICP.

Ultrasonography measurement of optic nerve sheath diameter is a simple, noninvasive, and reliable technique for intracranial pressure assessment. Studies have shown that there is a strong correlation between ultrasonographic measurements of ONSD and other cranial imaging methods or direct measurements of ICP.^[9,10]

The aim of our study is to investigate the effect of anesthesia management with propofol or ketofol in the ERCP procedure on the change in ICP, using ultrasonography measuring of optic nerve sheath diameter.

MATERIALS AND METHOD

Patients

This prospective, double-blinded, randomized, controlled study was approved by the Ankara City Hospital Human Research Ethics Committee before patient enrollment. Written informed consent was obtained. 132 patients belonging to the American Society of Anesthesiologists risk group I–III aged 18–80, scheduled for ERCP with sphincterotomy were included in the study from June to December 2021. Exclusion criteria were cases without sphincterotomy, history of optic nerve surgery, preexisting retinal detachment, glaucoma, or increased intraocular pressure. Procedure time that exceeds 90 minutes or is less than 30 minutes was also an exclusion criterion.

The cases were randomly enumerated in two sets with the help of randomizer.org and separated into two groups.

Group K: patients who were administered ketamine propofol mixture (ketofol) during sedation (n = 51).

Group P: patients administered propofol during sedation (n = 58).

Flow diagram of the study is shown in Figure 1.

Anesthetic protocols

Heart rate (HR), systolic arterial pressure (SAB), diastolic arterial pressure (DAB), mean arterial pressure (MAP), peripheral oxygen saturation (SpO2), respiratory rate (RR), bispectral index (BIS) and ETCO2 (capnography) were recorded by a researcher who was blinded to the groups.

All patients were administered 0,02 mg/kg iv. midazolam before the procedure.

In group K, Ketofol was prepared with 15 cc propofol %2 (1000 mg/50 ml concentration), 2 cc 50 mg/ml ketamine, and 13 cc serum saline into a 50 cc opaque syringe. (Ratio 1 mg of ketamine: 3 mg of propofol) This mixture is administered at a rate of 0.5 mL/kg/hr following a loading dose of 1 mg/kg (based on propofol) with an infusion pump. (Aitecs® syringe pump, 2016).

In group P, propofol 2% was prepared with 15 cc propofol and 15 cc serum saline in a 50 cc opaque syringe. After administering a loading dose of 1 mg/kg, the infusion was started at a rate of 0.5 mL/kg/hr using an infusion pump.

All patients were given 6 L/min of nasal oxygen, and flow was increased if necessary. In addition to the medication(s), all patients received continuous i.v. saline infusion (100 ml/h). ERCP was performed by the same gastroenterology doctor for all patients included in the study.

The procedure was started by inserting an endoscope at the 5^th minute of induction. 0.25 mg/kg propofol was administered intravenously via a separate route if BIS value was >85 or Wong-Baker FPS (Faces Pain Scale) >3 in both groups. The amount of additional propofol administered throughout the procedure was recorded.

Sonographic measurement of ONSD

Optic nerve sheath diameter (ONSD) measurement was performed by the researcher at T0: before induction, T1: after induction of anesthesia, T2: during sphincterotomy, T3: at the end of procedure following the removal of scope, and T4: after patient is fully awake, with a linear ultrasound transducer (Hitachi EUB-7000HV USG device) operating at 11 megahertz in B mode carefully to avoid excess pressure on the eye bulb. All measurements were made in the lateral decubitus position. An optimal USG image was obtained at 4 cm depth and ONSD was measured 3 mm behind the optic nerve head. Two measurements were made with the linear ultrasound transducer: transverse plane with horizontal placement and sagittal plane with vertical placement. The mean measurement values for both eyes with the anterior/lateral trans-bulbar approach were recorded. [Figure 2].

Endoscopic procedures

All cases were performed by the same endoscopist who has experience with ERCP for more than 10 years. A sufficient amount of ambient air was insufflated into the intestinal lumen to safely advance the endoscope and visualize the gastrointestinal tract, as needed by the endoscopist. An Olympus video duodenoscope (JF-260V; Olympus, Tokyo, Japan) was used in all procedures. Sphincterotome (CleverCut3™; Olympus, Tokyo, Japan) preloaded with a guidewire (0.025-inch VisiGlide 2; Olympus, Tokyo, Japan) and ENDO CUT I current mode in ERBE electrosurgical generator (VIO® 300 D; ERBE Elektromedizin, Tübingen, Germany) was used for cannulation and sphincterotomy.

Statistical analysis

IBM SPSS 25.0 and MedCalc 15.8 were used for data analysis. We used the Chi-square test and descriptive statistics to analyze study data. The data’s normal distribution was tested using Kolmogorov–Smirnov and graphical methods (histogram, Q-Q Plot, Stem and Leaf, Boxplot). For comparing normally distributed quantitative data between groups, we used t-tests for independent and dependent groups, as well as a repeated measures ANOVA test for within-group comparisons. Statistical significance level was accepted as P = 0.05. Power analysis was performed with the statistical package program G*Power 3.1.9.7 (Franz Faul, Universitat Kiel, Germany). The power of the study was found as 95% by n1 = 58, n2 = 51, α = 0.05, and effect size (d) = 0.70.

RESULTS

58 patients who were administered profopol and 51 patients who were administered ketofol for anesthesia management of ERCP were included in the study. Demographic characteristics of patients are summarized in Table 1. The mean age, body weight and BMI, gender distribution and comorbid disease rates, and mean ERCP procedure time were identical among patient groups (P > 0.05).

The mean height of the patients who received ketofol was taller (P < 0.05). Additional propofol dose requirement is significantly greater in Group P compared to Group K (median (Min-Max) 40 (0–140) vs0 (0–20), respectively).

In terms of ONSD values and changes through the course of procedure, no statistically significant difference (P > 0.05) was found between the groups. Both groups showed significantly greater variation from T0 to T2 compared to T0 to T1, T3 and T4, respectively (P = 0,000). T0 to T3 alteration was also significantly greater than T0 to T1 and T4 in both groups (P = 0,000). [Figure 3].

Although there was no statistically significant difference between the groups in terms of mean heart rate values, the heart rate value at T2 was significantly higher than T1 in both groups (96,3 ± 17,0 vs 87,3 ± 15,6 in Group P; P = 0,000 and 92,2 ± 15,6 vs 86,9 ± 13, 8 in Group K, respectively).

There was a statistically significant difference between the groups in terms of SpO2 and FPS values. SpO2 at T2 and T4 was significantly higher in group K [Table 2].

FPS at T1 and T2 was significantly higher in Group P [Figure 4].

BIS values within and between groups are shown in Table 3.

DISCUSSION

Endoscopic retrograde cholangiopancreatography (ERCP) is an endoscopic procedure for the diagnosis and treatment of biliopancreatic system diseases. During the procedure, the intestinal lumen is visualized by gas insufflation, and as a result, the intraluminal pressure rises. There are studies observing the systemic effects of intraluminal pressure in gastrointestinal system endoscopies. Many negative effects have been linked to an increase in intra-abdominal pressure caused by an increase in intraluminal pressure. These effects include a rise in systemic vascular resistance and venous pressure, a decrease in visceral and renal perfusion, changes in peak inspiratory pressure, and an increase in intracranial pressure.^[1-4,11-13] To our knowledge, this prospective, randomized, controlled, double-blind study including 109 patients is the first clinical study to investigate the change in intracranial pressure throughout the ERCP procedure under propofol and ketofol sedation. Our study clinically shows that intracranial pressure increases throughout the ERCP procedure, compatible with animal studies.

Propofol and ketofol both significantly reduce post-induction (T1) ONSD values compared to baseline ONSD (T0) measurements.

Neither agent was able to prevent the increase in ICP that occurred throughout the ERCP which is most notably during sphincterotomy.

Von Delius et al.^[13] showed that intra-abdominal pressure increases dramatically, lung compliance decreases with the effect of transdiaphragmatic pressure, tidal volume, and minute ventilation volume decrease, and inspiratory peak pressure increases after intraluminal air insufflation in the gastroscopy procedure.

Buscaglia et al.^[2] investigated potential changes in portal vein, IVC, intra-abdominal, and systemic pressures during various endoscopic procedures in a live pig model and found that the mean portal vein pressure during biliary sphincterotomy in the ERCP procedure alone was almost threefold compared to preprocedural pressure. In our study, we found a significant increase in ONSD measurement during sphincterotomy compared to all time sections. It is not clear whether this increase occurs because the procedure is painful and affects the level of sedation, or because of the hemodynamic effect of increasing portal vein pressure.

Avital et al.,^[3] in their experimental study on animals, showed that insufflation during colonoscopy increases intraperitoneal pressure and causes a significant increase in intracranial pressure.

Our study shows that the ERCP procedure increases intracranial pressure, possibly with similar mechanisms physiopathologically to these studies showing systemic effects of intra-abdominal pressure increase. This increase can be clinically significant for patients with comorbid liver damage who undergo sphincterotomy with the ERCP procedure. Patients at risk of hepatic encephalopathy may be more sensitive to increased intracranial pressure. However, it is unclear whether this increase has an effect on adverse clinical outcomes, and more studies are needed on measures to limit pressure increase in patients at risk.

In the literature, there are studies that monitor the increased intracranial pressure in laparoscopic and robotic surgeries with USG-guided ONSD technique.^[14] However, there is a lack of studies regarding the effects of ERCP procedure on intracranial pressure from such a standpoint.

Intra-abdominal insufflation pressure is standardized for laparoscopic surgery.^[13] However, there are no standard pressure data for GI endoscopy. Inadequate insufflation can result in incorrectly performed procedures, such as missing superficial cancer, and potentially lead to bleeding or perforation. On the other hand, excessive insufflation can cause serious side effects such as Mallory-Weiss syndrome, Boerhaave syndrome, and post-procedure pain and swelling.

Performing the procedure with manual air insufflation raises questions such as how much pressure is needed and whether the optimal pressure depends on the target organ or the patient’s disease/condition.^[1] As a result, there is not enough data on patient safety and optimal anesthesia management for anesthetists due to the lack of standard insufflation pressure determined for ERCP.

In our study, the mean ONSD levels measured before induction of anesthesia were found to be higher than the normal values for the supine position. This may be because the measurements were made in the lateral decubitus position. Body position affects intracranial and intraocular pressure due to multiple hemodynamic changes. During the ERCP procedure, the patient lies in the lateral decubitus position. Hwang et al.^[15] investigated the change in intraocular pressure after switching from the supine position to the lateral decubitus position during lung surgery and found an increase in the dependent eye. Malihi et al.^[16] investigated the effect of position on intraocular pressure in their study in young and healthy subjects, and they found an increase in intraocular pressure in the dependent eye when in the lateral decubitus position. Roth et al.^[17] found that lateral decubitus and prone position increased intracranial and intraocular pressure compared to the supine position in their study in the intensive care unit. Considering the results of these studies and since the studies in the literature are mostly in the supine position and a precise normal value cannot be specified, we thought that the current ONSD measurement values may mislead us. For this reason, we examined and analyzed the ONSD change rates.

In recent studies, insufficient sedation in the ERCP procedure has been associated with high failure rates due to patient discomfort and early termination of the procedure.^[18] It has been shown that the combination of ketamine and propofol in patients who underwent ERCP reduces the incidence of sedation-related complications and maintains hemodynamic stability with adequate sedation level.^[19] There are insufficient data on the effect of ketofol on intracranial pressure in the ERCP procedure. Ketofol is a mixture of ketamine and propofol in different ratios determined in the same syringe.

David H et al.^[20] have shown that the ketofol compound can be used successfully in combination with a single injector or in separate injectors. Calimaran A et al.^[21] stated that the mixture is chemically stable and safe to be mixed and used in the same injector. Based on these studies, we used ketamine and propofol in the same syringe. This ratio can be determined according to the undesirable effects of the drugs in the mixture (such as hemodynamic, respiratory, and delirium) and patient comorbidity. In the literature, the ketamine:propofol ratio has been used in different procedural processes in various ratios such as 1:1, 1:2, 1:3, and 1:5 according to mg. Hui et al.^[22] determined the ED50 of ketamine to be 0.39 mg/kg, and the ED50 of propofol to 1.1 mg/kg when used alone, and the ED50 of their combined use is ketamine 0.21 mg/kg and propofol 0.63 mg/kg. It was published as (1:3).

In the meta-analysis by Hayes et al.,^[23] ketofol mixtures applied in different procedures were examined in terms of side effects, and the ketamine-to-propofol ratio was reported as <1:3 in eight studies and ≥1:3 in 21 studies. The cutoff ratio of 1:3 was based on the most comprehensive systematic review and meta-analysis of the concomitant use of propofol ketamine for procedural sedation in adults in the emergency department.^[19]

Since this ratio is a reference and is frequently used, we prepared a ketofol mixture by mixing 15 cc of propofol 2%, 2 cc of ketamine 50 mg/ml, and 13 cc of serum saline in a 50 cc syringe and administered it to the patient as intravenous induction and maintenance infusion with a perfuser device.

Bhardwaj A et al.^[24] compared the combination of propofol and 1:5 mg ketofol for induction and maintenance of anesthesia in forty patients undergoing surgery following aneurysmal subarachnoid hemorrhage. An intraventricular catheter was placed and intraoperative ICP measurement was performed, and it was reported that the mean ICP values did not create a statistically significant difference between the two groups. (P = 0.802). It was reported that the intraoperative propofol requirement was significantly lower in the ketofol group. In addition, ketofol provided better hemodynamics during maintenance of anesthesia.

In our study, the rapid onset and short duration of the effect of propofol alone necessitated many additional doses during the procedure in group P (P < 0.001). These findings can be interpreted that ketofol reduces the need for additional anesthetic doses, causing less complications such as apnea and respiratory depression, and providing more effective sedation. Although BIS values were higher in ketofol group, this was due to the dissociative characteristics of ketamine. Comparably FPS values were higher in the propofol group in accordance with lower SPO2 values due to additional propofol requirement in our study.

One of the limitations of the study is that the minimum cut-off values of the ONSD showing increased intracranial pressure are not clear, as has been shown in previous studies.

The increase in ICP during ERCP mainly indicates the increase in intracranial pressure caused by increased intra-abdominal pressure or insufficient sedation. For this reason, in our study, the measurements were made by the same people, and the follow-up of the increase and decrease of the measurements was tried to be standardized.

Another limited aspect of our study is that the effect of the increase in ONSD levels, which cannot be limited by propofol and ketofol sedation applied during ERCP, on clinical patient outcomes was not investigated. Further studies are needed to question the clinical significance of this increase and to investigate the effect of deeper sedation or general anesthesia on the increase in ONSD during the ERCP procedure.

CONCLUSION

Intracranial pressure increases in ERCP procedures performed under propofol and ketofol sedation, mostly during sphincterotomy. Ketofol is recommended to be used as an appropriate agent in the management of ERCP anesthesia, as it complements the sympathomimetic and analgesic effects of ketamine and the limitations in the effectiveness of propofol and does not change the intracranial pressure in the direction of increase. Further studies are needed on the effectiveness of options such as general anesthesia or deeper sedation levels or reduction of insufflation pressure in patients at such risk.

Institutional review board statement

The present study was conducted after ethical approval from the Institutional Ethics Committee of Ankara City Hospital (Ethics No: E1/1786/2021, Date: 28.04.2021) and is registered with www.clinicaltrials.gov (identifier: NCT04910087).

Informed consent statement

A written informed consent was obtained from the participants for their willingness to participate in the study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

REFERENCES