Logo Medical Science Monitor

Call: +1.631.470.9640
Mon - Fri 10:00 am - 02:00 pm EST

Contact Us

Logo Medical Science Monitor Logo Medical Science Monitor Logo Medical Science Monitor

01 June 2024: Clinical Research  

Comparison of Fentanyl, Ketamine, and Lidocaine Combined with Propofol Anesthesia in Patients with Crohn Disease Undergoing Colonoscopy

Kamil Chudziński ORCID logo1ABCDEF, Konstanty Szułdrzyński ORCID logo1DEF, Miłosz Jankowski ORCID logo1CDEF, Kamil Adamczyk ORCID logo1EF*, Elżbieta Sokół-Kobielska2DEF

DOI: 10.12659/MSM.944116

Med Sci Monit 2024; 30:e944116

0 Comments

Abstract

0:00

BACKGROUND: Colonoscopy is the predominant invasive procedure for Crohn disease (CD) patients. Opioids and propofol carry risks of respiratory and cardiovascular complications. This study aimed to evaluate whether substituting fentanyl with ketamine or lidocaine could diminish propofol usage and minimize adverse events.

MATERIAL AND METHODS: In total, 146 patients with CD scheduled for elective colonoscopy were assigned to anesthesia with fentanyl (n=47), ketamine (n=47), or lidocaine (n=55). Propofol was administered to achieve sufficient anesthesia. Measured outcomes in each group included propofol consumption, hypotension and desaturation incidents, adverse event types, consciousness recovery time, abdominal pain intensity, Aldrete scale, and Post Anaesthetic Discharge Scoring System (PADSS).

RESULTS: Patients administered fentanyl needed significantly more propofol (P=0.017) than those on ketamine, with lidocaine showing no notable difference (P=0.28). Desaturation was significantly less common in the ketamine and lidocaine groups than fentanyl group (P<0.001). The ketamine group experienced milder reductions in mean arterial (P=0.018) and systolic blood pressure (P<0.001). Recovery metrics (Aldrete and PADSS scores) were lower for fentanyl (P<0.001), although satisfaction and pain levels were consistent across all groups (P=0.797). Dizziness occurred less frequently with lidocaine than fentanyl (17.2%, P=0.018) and ketamine (15.1%, P=0.019), while metallic taste incidents were more prevalent in the lidocaine group (13.5%, P=0.04) than fentanyl group.

CONCLUSIONS: Using ketamine or lidocaine instead of fentanyl in anesthesia for colonoscopy in patients with CD significantly lowers propofol use, reduces desaturation events, maintains blood pressure more effectively, without increasing hypotension risk, and accelerates recovery, without negatively impacting adverse events or patient satisfaction.

Keywords: Anesthesia and Analgesia, Colonoscopy, Inflammatory Bowel Diseases

Introduction

Crohn Disease (CD) is a chronic, idiopathic inflammatory disorder that primarily affects the gastrointestinal tract. Characterized by transmural inflammation that can span any segment from the mouth to the anus, CD presents a diverse range of clinical symptoms. Its etiology is multifactorial, involving a complex interplay of genetic predisposition, environmental factors, microbial flora, and the host immune system [1]. Colonoscopy plays a crucial role in diagnosing CD, enabling histopathological evaluation, and assessing the effectiveness of therapeutic interventions, particularly in achieving endoscopic remission and managing complications [2]. Recognized international gastroenterological societies advocate for periodic screening colonoscopies for patients with CD, with intervals varying between 1 and 5 years, based on individual risk factors [3,4].

Colonoscopy, like other invasive procedures, can cause discomfort, pain, anxiety, and fear [5]. The pain during colonoscopy primarily results from the stimulation of visceral pain receptors, especially in the rectum, intestinal mesentery, and peritoneal linings [3,5]. In patients with CD, colonoscopies often require extended duration and heightened operator expertise due to the increased risk of mechanical complications, such as intestinal perforation and bleeding, and elevated pain and anxiety levels, compared with colonoscopies in the general population [6].

In 2020, expert recommendations were issued for administering sedation and anesthesia to patients undergoing colonoscopy in hospital settings [7]. These indicate that the use of sedation in these patients is safe and improves their experiences related to the examination. For most patients, light or moderate sedation, during which contact with the patient is maintained throughout, is sufficient. The comfort of the sedated patient can also be enhanced by the following: prior education about the course of the examination, verbal communication during the procedure, the use of carbon dioxide instead of air for intestinal insufflation, thermal comfort, favorite music, and the presence of a loved one. The mentioned recommendations do not advise the routine use of deep sedation (general anesthesia) in patients undergoing colonoscopy in hospitals. Such patients remain unconscious during the examination, with diminished protective reflexes, but spontaneous breathing is maintained. The authors of the guideline emphasize considering the use of general anesthesia only in strictly selected patient groups and the necessity of ensuring vital signs monitoring and anesthetic care during its administration. They recommend introducing standard local protocols for this purpose.

In the context of drugs used for sedation in gastrointestinal endoscopy, the latest 2024 guidelines list drugs such as propofol, fentanyl, remimazolam, nitrous oxide, and pethidine as recommended drugs [8]. These guidelines do not reference the utilization of intravenous (i.v.) ketamine or lidocaine. Furthermore, the inclusion of pethidine in these recommendations appears to be a matter of debate, particularly because, for instance, in Poland, this drug was withdrawn from production due to a plethora of adverse effects [9–11].

Propofol, a rapidly acting i.v. anesthetic with a short duration, is commonly used for gastrointestinal endoscopy when titrated by an experienced anesthesiologist. Despite its frequent use, propofol lacks analgesic properties [7,12].

Fentanyl, widely used for general anesthesia induction, i.v. anesthesia, analgesia, and sedation, has a rapid onset and short duration but can accumulate with repeated administration. Patients with inflammatory bowel diseases, including CD, often rely on continuous analgesic therapy for chronic abdominal pain management. The gastrointestinal adverse effects of non-steroidal anti-inflammatory drugs restrict their use, leading to an increased prescription of opioids. Moreover, the greater the exposure to opioids (in any form) in hospitalized patients with inflammatory bowel disease, the higher doses of opioids subsequently prescribed in outpatient treatment [13]. Recently, non-opioid anesthesia techniques, such as ketamine and lidocaine, have become popular alternatives, offering reduced risks associated with opioid use [12,14]. Ketamine, a derivative of phencyclidine, is an anesthetic agent that exhibits unique and potent analgesic effects at subanesthetic doses of 0.1 to 0.5 mg/kg i.v. Its mechanism of action primarily involves the inhibition of the N-methyl-D-aspartate (NMDA) receptors, a crucial component in the nociception process. Additionally, ketamine exerts its effects through agonistic interactions with opioid receptors and by inhibiting the reuptake of catecholamines in the central nervous system. In contrast to gamma-aminobutric acid receptor type A agonists, such as benzodiazepines and propofol, as well as opioid receptor agonists, ketamine does not induce respiratory depression or diminish protective airway reflexes. Instead, it has the opposite effect – it stimulates respiration and dilates the bronchi. The bronchodilatory effects of ketamine are attributed to a multifaceted mechanism of action, involving the inhibition of the NMDA receptor-mediated airway constriction, a decrease in pulmonary nitric oxide levels through the suppression of inducible nitric oxide synthase, and an elevation in synaptic catecholamine levels due to the blockage of their presynaptic reuptake. Additionally, ketamine attenuates inflammation by reducing macrophage mobilization and cytokine release, inhibits vagal nerve activity, and facilitates direct smooth muscles relaxation by decreasing calcium influx through its channels [15,16]. By activating the sympathetic nervous system, ketamine ensures hemodynamic stability during anesthesia. Consequently, it can increase arterial blood pressure and cause tachycardia [15].

Lidocaine, by antagonistically acting on sodium channels, inhibits the depolarization of excitable cells, thereby finding application as both a local anesthetic and an antiarrhythmic agent. When administered intravenously, lidocaine enhances the effects of anesthetics, mitigates central hyperalgesia induced by opioids, and exhibits analgesic, anti-inflammatory, and immunomodulatory properties. It increases the respiratory center’s reactivity to hypercapnia, decreases laryngeal and bronchial reactivity, and enhances intestinal peristalsis. At therapeutic concentrations, lidocaine can exert a mild depressive effect on the cardiovascular system [17]. Both ketamine and lidocaine are key components in opioid-free anesthesia [18].

This study was designed with 2 objectives: 1) to evaluate whether replacing fentanyl (FNT) with ketamine (KET) or lidocaine (LID) could decrease the total propofol dosage required for colonoscopy in patients with CD, the primary outcome, and 2) to assess if opioid-free anesthesia, in comparison with FNT-based anesthesia, lowers the risk of respiratory and circulatory events, diminishes adverse events, and enhances patient satisfaction and post-anesthetic outcomes, the secondary outcomes.

Material and Methods

STUDY SETTING AND PARTICIPANTS:

This study and patients’ informed consent form received approval from the local Ethics Committee (decision number: 75/2018, date of issuance: August 1, 2018) and adhered to the ethical standards of the 2013 Declaration of Helsinki. It was conducted in patients with a diagnosis of CD who were undergoing an elective colonoscopy at the Endoscopy Laboratory of the Department of Gastroenterology and Internal Medicine at the National Medical Institute of the Ministry of the Interior and Administration in Warsaw, Poland.

The diagnosis of CD in all patients was made by experienced specialists of gastroenterology on the basis of clinical symptoms (abdominal pain, recurrent fevers, diarrhea, body weight loss, malnutrition, cachexia, anemia), biochemical and stool assessment, and endoscopic findings (skip lesions, with varying degrees of inflammation, including erythema, friability, erosions, and ulcers, next to areas of normal-appearing mucosa), confirmed with histopathological examination, according to ECCO-ESGAR guidelines [19].

The primary indication for colonoscopy in this patient group was the routine assessment of the gastrointestinal tract during pharmacological treatment (including biological treatment) or screening for colorectal cancer. The decision to perform colonoscopy under general anesthesia was based on patient preference, the endoscopist’s anticipation of potential technical challenges, or the need for extended procedure time.

Inclusion criteria comprised a confirmed diagnosis of CD and the provision of willing, informed consent for study participation. Exclusion criteria included patients with a classification as class III, IV, or V according to the American Society of Anesthesiologists (ASA) physical status classification system, those with a history of epilepsy or seizures, allergies to any of the anesthetic agents used, chronic liver or kidney diseases, a history of coronary artery disease or previous heart attacks, and circulatory instability requiring the use of vasoconstrictors or inotropic drugs.

INTERVENTION:

Upon acquiring written informed consent, patients were allocated in a 1: 1: 1 ratio using a mobile application (Randomizer for Clinical Trial by Regis Bournique for iOS platform). This app selected 1 of 3 codes from a finite pool, assigning patients to 1 of the following 3 groups: FNT at 1 μg/kg body weight (BW) i.v., KET at 0.5 mg/kg BW i.v., or LID at 1.5 mg/kg BW i.v.

Before undergoing colonoscopy, all eligible patients were premedicated with midazolam at a dosage of 0.02 mg/kg BW i.v., capped at a maximum of 2 mg. Anesthesia was initiated with an initial dose of 0.5 mg/kg BW of propofol i.v. This was supplemented as necessary with 1% propofol solution in 10 to 20 mg i.v. increments to maintain an adequate depth of general anesthesia, characterized by unconsciousness while preserving spontaneous breathing. The doses of the study drugs (FNT, KET, LID) were administered slowly and were not repeated during the procedure.

COLLECTED DATA AND OUTCOME MEASURES:

Before administering anesthesia, we collected demographic data (sex, age) and performed anthropometric measurements (BW and height) on eligible patients to calculate their body mass index (BMI). We also conducted an evaluation using ASA classification, alongside an assessment of concurrent medical conditions, and scrutinized inclusion and exclusion criteria.

During anesthesia, we measured the cumulative propofol consumption in milligrams, adjusted for BW and procedure duration. Respiratory and circulatory stability were monitored, and any complications were duly recorded.

Key respiratory and circulatory parameters, including peripheral oxygen saturation (SpO2), heart rate, electrocardiographic tracings, and noninvasive blood pressure (BP), were continuously monitored. BP readings (systolic, SBP; diastolic, DBP; mean arterial pressure, MAP) were taken at 3-min intervals. Initial values for heart rate and BP, recorded after premedication, were used for further analysis. Comprehensive details, such as monitored vital parameters, patient demographics, administered drug dosages, precise anesthesia timings, and patient transfer to the ward, were meticulously documented in the anesthesia record.

Respiratory stability was evaluated by noting episodes of desaturation, defined as a decrease in SpO2 below 90% for more than 30 s, including cases of severe desaturation necessitating airway interventions, such as the jaw-thrust maneuver or the use of an oropharyngeal airway.

In instances of hypotension (MAP decrease below 65 mmHg lasting at least 1 min), BP was measured every minute until MAP rose above 65 mmHg. Cases of severe hypotension, with MAP below 55 mmHg, were also documented. Absolute and relative changes in individual BP values (ΔMAP/ΔSBP/ΔDBP) compared with baseline were calculated. These hypotension thresholds were established based on universally recognized minimum perfusion pressures essential for organ viability (MAP below 65 mmHg) [20].

The period from the procedure’s end to the patient regaining consciousness (responding to verbal and tactile stimuli) was timed in seconds. Post-colonoscopy assessments included the modified Aldrete score [21] and the Post Anaesthetic Discharge Scoring System (PADSS) [22].

Upon returning to the ward, the patients anonymously completed a brief, encoded questionnaire, rating their anesthesia satisfaction and abdominal pain severity on numerical rating scales (NRS, 1–10 points) and reporting any adverse events. Patients could report multiple adverse events. Additionally, the subsequent hospitalization course was observed for respiratory (pneumonia) and circulatory complications (cardiac arrest, myocardial infarction, stroke), and any other fatalities.

STATISTICAL ANALYSIS:

For this study, all statistical computations and graphical representations of results were conducted using R software, version 4.0.2. Categorical variables were expressed as frequencies (percentages) and their comparisons were conducted with chi-square and Fisher’s exact tests, depending on the context. The normality of continuous variables was evaluated using the Shapiro-Wilk test. Variables conforming to a normal distribution were presented as means ± standard deviation (SD) and compared using the t test. Non-normally distributed data were described using medians and interquartile ranges (IQRs), and intergroup comparisons were performed using the Kruskal-Wallis test, supplemented with the Dunn post hoc analysis and Bonferroni adjustment for multiple comparisons.

To explore predictive factors for the administered dose of propofol, multivariable linear regression models were used. For the assessment of specific events, such as desaturation and hypotension, logistic regression models were used to calculate odds ratios (ORs) with 95% confidence intervals (CIs). The analysis commenced with single-variable models, which subsequently informed the development of multivariable models, optimized using stepwise backward elimination. In these models, categorical variables were assigned reference values, with sex referenced to male and group to FNT. Statistical significance was determined at P values less than 0.05.

The sample size was determined using SPSS (IBM Corp, Armonk, NY, USA) for comparison of the 3 groups using one-way ANOVA, with the primary outcome being total propofol consumption. Retrospectively based on our previous pilot study involving 20 patients receiving FNT, the mean of total propofol consumption was 140 mg (SD: 37.5 mg). An anticipated difference of 15% between the groups was expected, corresponding to a total propofol dose of 119 mg in patients treated with KET and LID. The required sample size for each group was 48, considering a significance level of 0.05 and statistical power of 80%. Assuming a loss of follow-up of 15%, 55 patients were required per group, and a total of 165 patients was finally included.

Results

ANESTHESIA COURSE, ADVERSE EVENTS, AND SATISFACTION IN ALL ANALYZED PATIENTS:

The average duration of colonoscopy in this study was 15.25 min, with an SD of 7.05 min. Patients under anesthesia received an average of 121.23 mg of propofol (SD: 51.02 mg), equating to a BW-adjusted average dose of 0.12 mg/kg/min (SD: 0.05 mg/kg/min).

Desaturation events were noted in 27 (18.5%) patients, with 18 (12.3%) experiencing this within the first 5 min of anesthesia. Severe desaturation was observed in 2 patients, accounting for 1.4% of the total participants.

MAP values dropped below 65 mmHg in 22 patients (15.1%), with varying frequency of hypotension episodes. Severe hypotension, characterized by MAP falling below 55 mmHg, was recorded in 5 patients (3.4%). The average decreases in MAP during anesthesia were 7.34 mmHg (SD: 10.96 mmHg) in absolute terms and 7.3% (SD: 11.31%) in relative terms. The mean changes in SBP (ΔSBP) and DBP (ΔDBP) were −12.4 mmHg (SD: 13.15 mmHg) and −9.1% (SD: 9.82%) for SBP, and −4.8 mmHg (SD: 12.63 mmHg) and −3.93% (SD: 12.91%) for DBP. In hypotensive episodes, the mean decreases were 11.77 mmHg (SD: 10.87 mmHg) or 24.41% (SD: 0.96%) for MAP, −23.91 mmHg (SD: 9.54 mmHg) or −24.72% (SD: 3.56%) for SBP, and −15.59 mmHg (SD: 11.08 mmHg) or −28.34% (SD: 8.37%) for DBP.

Recovery time to consciousness after procedure ranged from immediate (0 s) to 320 s. The median Aldrete score was 10 (IQR: 9–10), and PADSS was 9 (IQR: 8–10).

Patient satisfaction with anesthesia, rated on the NRS, where 0 is ‘very dissatisfied’ and 10 is ‘very satisfied’, had a median of 10 (IQR: 10–10).

Post-colonoscopy abdominal pain was reported by 28.8% of patients (n=42), with a median pain intensity of 3 on the NRS (IQR: 1.25–5.75), where 0 indicates ‘no pain’ and 10 signifies ‘unbearable pain’.

Adverse events occurred in 43 (29.5%) of the patients, with transient regaining of consciousness during the procedure reported by 27 (18.8%) participants. The most frequently reported symptoms were dizziness (37.5%, n=18), metallic taste in the mouth (16.7%, n=8), and nausea and vomiting (16.7%, n=8).

There were no fatalities either during the procedures or throughout the hospitalization period.

COMPARISON OF ASSESSED ANALGESIA METHODS AND PREDICTORS OF OUTCOMES:

In our study, the 3 patient groups – FNT, KET, and LID – were comparable in demographic and baseline clinical characteristics, including age, sex distribution, weight, height, BMI, initial BP, heart rate, and colonoscopy duration. Furthermore, the analysis revealed no significant differences among these groups in several key areas: patient satisfaction with the administered anesthesia, presence, and severity of abdominal pain after the procedure, overall frequency of adverse events during or after the procedure, and instances of brief awakenings during anesthesia. Additionally, the groups did not show significant differences in the occurrence of hypotension (inclusive of severe cases), average decrease in BP during hypotension episodes, and mean changes in diastolic BP (ΔDBP), as shown in Table 1.

However, statistically significant differences were noted among the anesthesia groups in relation to several critical variables:

The specific variations between the anesthesia groups are detailed in Table 2, which provides a thorough pairwise comparison across the different study parameters.

TOTAL PROPOFOL DOSE:

Patients in the FNT group required significantly higher doses of propofol: 20.8% more in milligrams (P=0.017, 95% CI: 5.77–36.5%) and 28.6% more on a mg/kg BW per minute basis (P<0.001, 95% CI: 14.3–42.9%), compared with those receiving KET. In contrast, no significant difference in propofol dosage was observed between the LID and FNT groups (as illustrated in Table 2 and Figure 2).

To further understand propofol consumption patterns, multivariate linear regression models were developed, considering factors such as age, sex, BMI, the specific anesthesia group, and duration of the procedure (Table 3).

The regression analysis revealed a direct correlation between prolonged colonoscopy duration and increased propofol usage, with an additional 4.56 mg of propofol needed per extra minute of the procedure. Propofol consumption decreased with patient age, showing a reduction of about 1.19 mg for each additional year. Both the KET and LID groups required significantly less propofol than the FNT group, by 41.5 mg and 25.5 mg, respectively. It is important to note that these predictive estimates assume the constancy of other factors included in the model.

The dose of propofol expressed in mg/kg BW/min showed significant associations with variables such as age, BMI, KET usage, and procedure duration, as detailed in Table 4.

RESPIRATORY STABILITY:

We observed a significantly higher frequency of desaturation events, particularly in the initial 5 min of anesthesia, in the FNT group than in the KET and LID groups (P<0.05, as shown in Table 1). This trend of early-onset desaturation was common across all groups. However, there was no notable difference in the likelihood of severe desaturation episodes among the groups (P=0.204), and none of the patients required bag-valve-mask ventilation or experienced pneumonia during their hospital stay.

Table 5 details logistic regression models that elucidate the factors influencing desaturation during the study. The univariate analysis indicated that the risk of desaturation was significantly associated with patient age, BMI, anesthesia group, and administered dose of propofol (mg). In the multivariate analysis, each 1 kg/m2 increase in BMI and each additional minute of colonoscopy were linked with 1.20- and 1.05-times greater odds of experiencing desaturation, respectively. Notably, the probability of desaturation in the KET and LID groups was substantially lower, with odds 20 times less than that in the FNT group.

CARDIOVASCULAR STABILITY:

In this study, no severe cardiovascular events, including myocardial infarction or stroke, were recorded among the patients. Additionally, the incidence of hypotension was not significantly different across the study groups. However, notable differences were observed in the MAP and SBP changes during anesthesia. Specifically, the alterations in ΔMAP and ΔSBP were statistically significant (P<0.05 and P<0.001, respectively), although these variances were not mirrored in the DBP changes or the average BP reductions when hypotension occurred.

In-depth post hoc analysis revealed that the decreases in MAP and SBP were significantly less in the KET group than in the FNT group. In the KET group, the MAP reduction was on average 4.42 mmHg less (P=0.018; 95% CI: −8.89–−0.22), amounting to a mean relative difference of 5.34% (P=0.0106; 95% CI: −9.85–−0.65%). The SBP decrease was also lower in the KET group by an average of 9.55 mmHg (P<0.001; 95% CI: −13.92–−5.08), equating to a 7.65% reduction (P<0.001; 95% CI: −11.06–−4.20%). Furthermore, the KET group exhibited a significantly smaller drop in SBP than did the LID group, with an absolute mean difference of 6 mmHg (P=0.0271; 95% CI: 0.81–11.27) and a relative difference of 4.48% (P=0.0168; 95% CI: 0.62–8.32%). No significant differences in SBP changes were observed between the LID and FNT groups (P>0.05).

ADVERSE EVENTS:

While the overall occurrence of adverse events was comparable across all anesthesia groups, as shown in Figure 3, the specific types of events varied in frequency depending on the anesthesia used.

Notably, there were statistically significant variations in the incidence of dizziness and the sensation of a metallic taste among the groups (P<0.01). In-depth post hoc analysis revealed a markedly lower incidence of dizziness in patients receiving LID than in those given FNT (a 17.2% decrease, P=0.018; 95% CI: 3.3–31.1%) and KET (a 15.1% decrease, P=0.019; 95% CI: 1.7–28.5%). Furthermore, the LID group reported experiencing a metallic taste significantly more often than did the FNT group, with a 13.5% higher occurrence (P=0.04; 95% CI: 24.8–2.2%). This distinction in the frequency of specific adverse events underscores the varied adverse effect profiles of the anesthesia agents used.

POST-ANESTHESIA PATIENT CONDITION:

The study revealed that patients anesthetized with FNT experienced notably prolonged durations to regain consciousness after colonoscopy than did those in the KET and LID groups, as shown in Table 1 and Figure 4. Additionally, the FNT group exhibited significantly lower recovery scores, as assessed by both the Aldrete and PADSS scales, relative to the KET and LID groups. However, it is noteworthy that patient satisfaction with the anesthesia, as well as the frequency and intensity of post-procedural abdominal pain, did not significantly differ across the groups. This suggests that while FNT can affect recovery times and scores, it does not adversely affect overall patient satisfaction or post-colonoscopy abdominal discomfort.

Discussion

PROPOFOL-SPARING EFFECT:

In our study, direct comparisons between groups revealed that the dose of propofol was significantly lower for patients anesthetized with KET than for those who received FNT. Regression analyses further corroborated the propofol-conserving effects of KET and LID, with FNT serving as the reference standard.

These results align with the current body of research, which suggests KET can decrease propofol requirements in colonoscopy anesthesia by approximately 19% to 32.6% [23–25]. The magnitude of this reduction is influenced by factors including the dosage of KET, ratio of KET to propofol, concurrent administration of other medications, and specific nature of the procedure [26].

The literature also indicates that LID can reduce propofol needs during colonoscopy anesthesia, although the evidence is less uniform than that for KET, showing greater variance [27–30]. For instance, Forster et al reported a 50% reduction in total propofol use with LID infusion, whereas Li et al observed only a 13.2% decrease [27,28]. Such variation could be attributed to the LID dosage, usage of additional drugs, and patient demographics. A meta-analysis encompassing 12 randomized trials confirmed that LID decreases propofol consumption for gastrointestinal endoscopy, including colonoscopy [30]. Nevertheless, this meta-analysis also highlighted the heterogeneity in study quality and called for more research to definitively ascertain the role of LID in conserving propofol in the context of colonoscopy anesthesia.

RESPIRATORY EVENTS:

Respiratory complications are a known risk during anesthesia for gastrointestinal endoscopy, although they are typically transient. Strategies that lower propofol use and omit opioids can diminish the likelihood of such events [30–34]. Agents such as KET and LID have been shown to conserve propofol usage while enhancing respiratory response to carbon dioxide [14]. In line with these findings, our study indicates that desaturation occurred more frequently in patients administered FNT than in those given KET or LID. This outcome implies that FNT may be a significant contributory factor to desaturation risks in patients with CD undergoing colonoscopy. In evaluating the implications of our findings, it is imperative to consider the research conducted by Aminnejad et al [35], which assessed the efficacy and safety of a dexmedetomidine/KET combination, compared with that of a propofol/FNT regimen in sedation during colonoscopies. This study elucidated that dexmedetomidine/KET, despite a moderately lower mean sedation score and similar satisfaction of gastroenterologist and patients’ pain score, significantly reduced the incidence of severe complications, such as hypotension and apnea. It is crucial to note that in the Aminnejad et al study, the effects of KET were evaluated in conjunction with dexmedetomidine, rather than propofol, as in our investigation. Edalatkhah et al, in comparing 3 drug combinations for anesthesia for colonoscopy, showed that the use of propofol with FNT, KET, and LID was associated with a lower incidence of respiratory events (cough, apnea, need for jaw thrust) than was the use of propofol with FNT or propofol with FNT and LID [36].

CARDIOVASCULAR EVENTS:

The relationship between propofol dosage and the occurrence or severity of hypotension during colonoscopy anesthesia remains ambiguous. Sneyd et al [37] reported that 36% of patients undergoing propofol anesthesia for colonoscopy experienced hypotension, with both the depth and duration correlating with the propofol amount administered. Nonetheless, the clinical significance of hypotension during sedative procedures can differ from that during surgery. In contrast, a double-blind, placebo-controlled study discerned no variation in hypotension frequency when comparing KET-propofol, FNT-propofol, and propofol-only groups during colonoscopy anesthesia [38]. Similarly, a meta-analysis indicated that adjunctive i.v. LID with propofol for gastrointestinal endoscopies does not alter hypotension risk, although it reduces propofol requirements [30].

In our study, the KET group exhibited significantly less decline in MAP and SBP than did the FNT group; however, no disparities in hypotension risk were found, and the overall propofol dosage did not affect hypotension risk, even when defined as a MAP decrease exceeding 20%. This finding is at odds with the meta-analysis by Sneyd et al, which demonstrated a connection between propofol dose and hypotension [37]. The discrepancy might stem from the present study’s inclusion of younger patients with chronic conditions but without serious cardiovascular comorbidities, as opposed to Sneyd et al’s meta-analysis, which primarily included patients of ASA class III. Moreover, the meta-analysis used a more sensitive threshold for hypotension (SBP <90 mmHg), potentially accounting for the higher incidence of detected hypotension events.

In light of the recent findings by Yin et al [39], who explored the efficacy and tolerability of adding various agents to propofol-based sedation in elderly patients undergoing gastrointestinal endoscopy, there are several noteworthy considerations to juxtapose with our study. Yin et al reported that the combination of propofol with KET at a dose of 0.4 mg/kg maintained hemodynamic and respiratory stability in elderly patients, evidenced by reduced incidences of hypotension, bradycardia, and hypoxia. This agrees with our observation of less decline in MAP and SBP in the KET group, albeit in a different patient demographic.

POST-ANESTHESIA PERIOD:

In the present study, KET and LID demonstrated non-inferiority to FNT regarding recovery metrics after colonoscopy. Patients receiving these agents regained consciousness more swiftly and attained higher Aldrete and modified PADSS scale scores than did those given FNT, with the statistical significance of these findings tempered by a small effect size, suggesting limited clinical relevance. High levels of patient satisfaction with the anesthetic experience were reported across all groups, notwithstanding the occurrence of adverse events and post-procedural abdominal discomfort.

Dizziness was the most commonly reported adverse effect, less prevalent in the LID group than in those receiving FNT or KET, reflecting the known adverse effect profiles of these drugs [12]. A metallic taste, frequently associated with LID, was observed significantly more often with its use, although it was transient and not indicative of toxicity.

The similarity in post-anesthetic symptomatology and overall health status among the 3 anesthesia modalities indicates their potential for safe application in outpatient settings. These conclusions agree with existing literature on anesthesia for colonoscopy [24,34].

STUDY STRENGTHS AND LIMITATIONS:

This study’s primary strengths lie in its meticulous evaluation of anesthesia outcomes in patients with CD during colonoscopy and the comparative analysis of the effects of FNT, KET, and LID within a propofol-based anesthesia regimen. This is particularly pertinent given that most prior research has investigated opioid-free anesthesia across a general patient demographic referred for intestinal endoscopy. Consequently, our insights – especially those regarding the mitigation of desaturation risks and reduced propofol dosage through opioid-free methods – hold significant implications for the clinical management of CD, where colonoscopies are routinely conducted and are often challenged by increased pain and technical complexities.

However, this study does face a number of limitations that warrant consideration. The cohort primarily consisted of relatively young and medically stable individuals, deliberately excluding those classified as high-risk (ASA III and IV), which limits the generalizability of our findings. Comparisons were drawn against an FNT-propofol anesthetic baseline, rather than propofol as a standalone agent, potentially amplifying the perceived benefits of KET and LID on propofol conservation. Additionally, anesthesia depth was gauged by clinical observation rather than by objective sleep monitoring technologies, which may have affected the administration rates of propofol and adjunctive medications. It is worth noting that KET is known to increase bispectral index values, which could render sedation depth assessments based on this metric less reliable [40]. Moreover, respiratory assessments were clinically determined by observing chest movements and impedance variations, whereas capnometry-integrated facemasks might have provided a more accurate and earlier detection of apneic events. Lastly, this study was conducted within a single institution, and the findings might not be fully representative of broader clinical practices or patient demographics. This inherent limitation can potentially influence the applicability of our results in diverse healthcare settings, thus necessitating caution when extrapolating our conclusions to wider clinical contexts. Future studies involving multi-center trials are recommended to confirm our findings and enhance their generalizability.

Conclusions

This study revealed that substituting FNT with KET or LID in colonoscopy anesthesia for patients with CD resulted in a substantial reduction in propofol dosage and markedly diminished the incidence of desaturation events. Notably, patients anesthetized with KET exhibited less pronounced decreases in MAP and SBP relative to those receiving FNT, without any significant differences in hypotension risk, including its severe manifestation. Moreover, the use of KET or LID facilitated more rapid recovery from anesthesia, with no consequential escalation in adverse events or decrease in patient satisfaction levels.

References

1. Feuerstein JD, Cheifetz AS, Crohn disease: Epidemiology, diagnosis, and management: Mayo Clin Proc, 2017; 92(7); 1088-103

2. Zhao M, Gönczi L, Lakatos PL, Burisch J, The burden of inflammatory bowel disease in Europe in 2020: J Crohns Colitis, 2021; 15(9); 1573-87

3. Friedman S, Cheifetz AS, Farraye FA, Factors that affect adherence to surveillance colonoscopy in patients with inflammatory bowel disease: Inflamm Bowel Dis, 2013; 19(3); 534-39

4. Clarke WT, Feuerstein JD, Colorectal cancer surveillance in inflammatory bowel disease: Practice guidelines and recent developments: World J Gastroenterol, 2019; 25(30); 4148-57

5. Trevisani L, Zelante A, Sartori S, Colonoscopy, pain and fears: Is it an indissoluble trinomial?: World J Gastrointest Endosc, 2014; 6(6); 227

6. Weber AT, Ather N, Tran V, Higher sedation requirements among inflammatory bowel disease patients undergoing colonoscopy for disease activity assessment or dysplasia surveillance: Crohns Colitis 360, 2019; 1(1); OTZ006

7. Dossa F, Dubé C, Tinmouth J, Practice recommendations for the use of sedation in routine hospital-based colonoscopy: BMJ Open Gastroenterol, 2020; 7(1); e000348

8. Sidhu R, Turnbull D, Haboubi H, British Society of Gastroenterology guidelines on sedation in gastrointestinal endoscopy: Gut, 2024; 73(2); 219-45

9. Moy KV, Ma JD, Best BM, Atayee RS, Factors impacting variability of the urinary normeperidine-to-meperidine metabolic ratio in patients with chronic pain: J Anal Toxicol, 2014; 38(1); 1-7

10. Alsmadi MM, Idkaidek N, The analysis of pethidine pharmacokinetics in newborn saliva, plasma, and brain extracellular fluid after prenatal intrauterine exposure from pregnant mothers receiving intramuscular dose using PBPK modeling: Eur J Drug Metab Pharmacokinet, 2023; 48(3); 281-300

11. Brown C, Deiner S, Perioperative cognitive protection: Br J Anaesth, 2016; 117(Suppl 3); iii52-iii61

12. Goudra B, Gouda G, Mohinder P, Recent developments in drugs for GI endoscopy sedation: Dig Dis Sci, 2020; 65(10); 2781-88

13. Dalal RS, Palchaudhuri S, Snider CK, Exposure to intravenous opioids is associated with future exposure to opioids in hospitalized patients with inflammatory bowel diseases: Clin Gastroenterol Hepatol, 2020; 18(10); 2269-78e3

14. Barrett W, Buxhoeveden M, Dhillon S, Ketamine: A versatile tool for anesthesia and analgesia: Curr Opin Anaesthesiol, 2020; 33(5); 633-38

15. Barrett W, Buxhoeveden M, Dhillon S, Ketamine: A versatile tool for anesthesia and analgesia: Curr Opin Anaesthesiol, 2020; 33(5); 633-38

16. La Via L, Sanfilippo F, Cuttone G, Use of ketamine in patients with refractory severe asthma exacerbations: Systematic review of prospective studies: Eur J Clin Pharmacol, 2022; 78(10); 1613-22

17. Beaussier M, Delbos A, Maurice-Szamburski A, Perioperative use of intravenous lidocaine: Drugs, 2018; 78(12); 1229-46

18. Beloeil H, Opioid-free anesthesia: Best Pract Res Clin Anaesthesiol, 2019; 33(3); 353-60

19. Maaser C, Sturm A, Vavricka SR, ECCO-ESGAR guideline for diagnostic assessment in IBD Part 1: Initial diagnosis, monitoring of known IBD, detection of complications: J Crohns Colitis, 2019; 13(2); 144-164K

20. Saugel B, Sessler DI, Perioperative blood pressure management: Anesthesiology, 2021; 134(2); 250-61

21. Aldrete JA, The post-anesthesia recovery score revisited: J Clin Anesth, 1995; 7(1); 89-91

22. Chung F, Chan VWS, Ong D, A post-anesthetic discharge scoring system for home readiness after ambulatory surgery: J Clin Anesth, 1995; 7(6); 500-6

23. Upadya M, Neeta S, Brar G, Effect of ketamine and fentanyl in combination with midazolam and propofol during outpatient colonoscopy - a randomised controlled trial: J Clin Diagn Res, 2018; 12(9); UC05-UC09

24. Tuncali B, Pekcan YO, Celebi A, Zeyneloglu P, Addition of low-dose ketamine to midazolam-fentanyl-propofol-based sedation for colonoscopy: A randomized, double-blind, controlled trial: J Clin Anesth, 2015; 27(4); 301-6

25. Zhan Y, Liang S, Yang Z, Efficacy and safety of subanesthetic doses of esketamine combined with propofol in painless gastrointestinal endoscopy: A prospective, double-blind, randomized controlled trial: BMC Gastroenterol, 2022; 22(1); 391

26. Jalili M, Bahreini M, Doosti-Irani A, Ketamine-propofol combination (ketofol) vs propofol for procedural sedation and analgesia: Systematic review and meta-analysis: Am J Emerg Med, 2016; 34(3); 558-69

27. Forster C, Vanhaudenhuyse A, Gast P, Intravenous infusion of lidocaine significantly reduces propofol dose for colonoscopy: A randomised placebo-controlled study: Br J Anaesth, 2018; 121(5); 1059-64

28. Li M, Ke W, Zhuang S, Effect of intravenous lidocaine on propofol consumption in elderly patients undergoing colonoscopy: A double-blinded, randomized, controlled trial: BMC Anesthesiol, 2022; 22(1); 61

29. Chen M, Lu Y, Liu H, The propofol-sparing effect of intravenous lidocaine in elderly patients undergoing colonoscopy: A randomized, double-blinded, controlled study: BMC Anesthesiol, 2020; 20(1); 132

30. Hung KC, Yew M, Lin YT, Impact of intravenous and topical lidocaine on clinical outcomes in patients receiving propofol for gastrointestinal endoscopic procedures: A meta-analysis of randomised controlled trials: Br J Anaesth, 2022; 128(4); 644-54

31. Gupta K, Nagappa M, Prasad A, Risk factors for opioid-induced respiratory depression in surgical patients: a systematic review and meta-analyses: BMJ Open, 2018; 8(12); e024086

32. Wernli KJ, Brenner AT, Rutter CM, Inadomi JM, Risks associated with anesthesia services during colonoscopy: Gastroenterology, 2016; 150(4); 888-94

33. Qadeer MA, Lopez AR, Dumot JA, Vargo JJ, Hypoxemia during moderate sedation for gastrointestinal endoscopy: Causes and associations: Digestion, 2011; 84(1); 37-45

34. Li X, Lv X, Jiang Z, Application of intravenous lidocaine in obese patients undergoing painless colonoscopy: A prospective, randomized, double-blind, controlled study: Drug Des Devel Ther, 2020; 14; 3509-18

35. Aminnejad R, Hormati A, Shafiee H, Comparing the efficacy and safety of dexmedetomidine/ketamine with propofol/fentanyl for sedation in colonoscopy patients: A doubleblinded randomized clinical trial: CNS Neurol Disord Drug Targets, 2022; 21(8); 724-31

36. Edalatkhah S, Hazrati E, Hashemi M, Evaluation of anesthesia quality with three methods: “propofol + fentanyl” vs. “propofol + fentanyl + lidocaine” vs. “propofol + fentanyl + lidocaine + ketamine” in patients referred to the scoping ward: J Family Med Prim Care, 2022; 11(2); 672

37. Sneyd JR, Absalom AR, Barends CRM, Jones JB, Hypotension during propofol sedation for colonoscopy: A retrospective exploratory analysis and meta-analysis: Br J Anaesth, 2022; 128(4); 610-22

38. Kovačević M, Rizvanović N, Adilović A, Ketamine as the main analgesic agent during analgesia-based sedation for elective colonoscopy – a randomised, double-blind, control study: Saudi J Anaesth, 2022; 16(4); 423

39. Yin S, Hong J, Sha T, Efficacy and tolerability of sufentanil, dexmedetomidine, or ketamine added to propofol-based sedation for gastrointestinal endoscopy in elderly patients: A prospective, randomized, controlled trial: Clin Ther, 2019; 41(9); 1864-77e0

40. Carrara L, Nault M, Morisson L, The impact of bolus versus continuous infusion of intravenous ketamine on bispectral index variations and desflurane administration during major surgery: The KETABIS study: Eur J Anaesthesiol, 2021; 38(11); 1168-79

In Press

Review article  

Optimizing Quality of Life in Kidney Transplant Recipients Through Structured Exercise: A Systematic Review...

Med Sci Monit In Press; DOI: 10.12659/MSM.943617  

Clinical Research  

Ultrasound-Guided PRP and SVF Therapy Shows Sustained Improvement in Severe Knee Osteoarthritis: A 12-Month...

Med Sci Monit In Press; DOI: 10.12659/MSM.943975  

Clinical Research  

Olfactory Dysfunction as a Marker for Cognitive Impairment in General Paresis of the Insane: A Clinical Study

Med Sci Monit In Press; DOI: 10.12659/MSM.944243  

Clinical Research  

Endoscopic and Microscopic Tympanoplasty for Adhesive Otitis Media: A Comparative Prospective Analysis

Med Sci Monit In Press; DOI: 10.12659/MSM.945152  

Most Viewed Current Articles

17 Jan 2024 : Review article   4,462,997

Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron Variant

DOI :10.12659/MSM.942799

Med Sci Monit 2024; 30:e942799

0:00

14 Dec 2022 : Clinical Research   1,599,717

Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase Levels

DOI :10.12659/MSM.937990

Med Sci Monit 2022; 28:e937990

0:00

16 May 2023 : Clinical Research   691,092

Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...

DOI :10.12659/MSM.940387

Med Sci Monit 2023; 29:e940387

0:00

01 Jan 2022 : Editorial   50,889

Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...

DOI :10.12659/MSM.935952

Med Sci Monit 2022; 28:e935952

0:00

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750