Sedation in endoscopy: Finding the balance between safety and efficacy

Abstract

Sedation is the standard of care in gastrointestinal (GI) endoscopy in most institutions. Various protocols are employed to ensure a comfor patient experience and a high procedural success rate. Benzodiazepines combined with opioids are the most commonly used methods. However, these drugs have been associated with numerous adverse effects, including respiratory depression, hypoxia, and hypotension. Cohen et al conducted a study in this issue demonstrating the ability to minimize or eliminate opioid use without compromising procedural success rate or patient comfort. In this editorial, we explore the diverse sedation methods employed in GI procedures, assess the efficacy and safety of the drugs used, and highlight best practices

Key Words: Anesthesia; Colonoscopy; Endoscopy; Fentanyl; Gastroscopy; Midazolam; Propofol; Sedation

Core Tip: Optimizing sedation in gastrointestinal endoscopy requires a careful balance of efficacy and safety, tailored to individual patient needs and procedural demands. Recent insights suggest that midazolam as a standalone agent can achieve comparable patient satisfaction and safety profiles to the traditional midazolam-fentanyl combination, potentially reducing the risk of opioid-related complications.

INTRODUCTION

Gastrointestinal (GI) procedures, such as esophagogastroduodenoscopy (EGD) and colonoscopy, can be highly unpleasant and uncomfortable for patients. Common adverse symptoms include abdominal pain, bloating, and cramping during colonoscopy, as well as gagging and a choking sensation during EGD[1]. Consequently, sedation is paramount to ensure patient comfort, enhance procedural completion rates, and augment the likelihood of patients undergoing endoscopies again[2]. Sedation practices exhibit significant variations across countries and institutions. While sedation-related complications are relatively prevalent, they are generally transient. However, they can pose substantial risks when they do occur, primarily affecting the cardiovascular and respiratory systems[3]. Risk factors for these complications encompass not only patient-specific variables such as age and comorbidities, but most notably, the depth of sedation influenced by the type, dosage, and method of administering sedative drugs. Achieving optimal sedation necessitates tailoring the depth of sedation to the specific requirements of the patient and the procedure being performed. This delicate balance, precision, and occasional challenge demands meticulous attention.

CLASSIFICATION OF SEDATION LEVELS AND BACKGROUND

According to the American Society of Anesthesiologists (ASA), sedation levels are a continuum ranging from minimal sedation to general anesthesia[4]. Minimal sedation, or anxiolysis, maintains patients’ full responsiveness and intact respiratory and cardiovascular functions. Moderate sedation, or conscious sedation, reduces consciousness while preserving the ability to respond to verbal and tactile stimuli. Spontaneous breathing and cardiovascular functions are preserved. Deep sedation induces a state where patients are difficult to awaken but may respond to repeated or painful stimuli. Spontaneous breathing may be impaired, and airway support may be necessary. Cardiovascular function typically remains intact. General anesthesia entails the loss of consciousness, often necessitating ventilatory and cardiovascular support.

The mode of sedation is influenced by various factors, including patient characteristics, the complexity of the procedure, and institutional capabilities. While individual responses cannot always be accurately predicted, the same sedative dosage may result in varying perceived experiences[5]. The ultimate objective is to ensure patient comfort, minimize memory of the procedure, and achieve technical success without compromising safety.

Sedative agents: Efficacy and side effects

Routine endoscopic GI procedures can be performed with moderate sedation, it has been demonstrated to be effective and safe[6]. Cardiopulmonary complication rates were reported to be low, ranging from 0.05% to 0.10% for both upper and lower endoscopy[7,8]. This typically involves the use of a benzodiazepine alone or in combination with an opioid analgesic due to their complementary and synergistic effects. Below is a brief description of the effects and Table 1 summarizes their key characteristics.

Table 1 This table summarizes the key characteristics of each sedative agent.

Sedative agent	Overview	Onset of action	Duration of action	Adverse effects	Reversal agent	Key advantage	Key disadvantage
Benzodiazepines	Commonly utilized for sedation	Rapid	Short	RD	Flumazenil	Effective sedation, amnestic properties	Risk of RD
Opioids	Analgesic and sedative effects	Faster than meperidine	Shorter than meperidine	RD, bradycardia, hypotension	Naloxone	High potency	High risk of SAE
Propofol	Stands out for quick recovery	Prompt	Short	Cardiopulmonary complications, narrow therapeutic window	None available	Superior satisfaction, low safety concerns, quick recovery	Require careful titration, potential for SAE
Remimazolam	Short acting benzodiazepines	Rapid	Very short	Nausea, vertigo, prolonged recovery	None available	Water soluble, high success rates	Potential for SAE

RD: Respiratory depression; SAE: Serious adverse effects.

Benzodiazepines: Benzodiazepines like midazolam and diazepam are commonly used. Both are sedative, but midazolam is preferred for its faster onset, shorter duration, and strong amnestic properties[9,10]. Respiratory depression can be a serious side effect. Flumazenil, a specific benzodiazepine antagonist, quickly reverses hypnotic and sedative effects[11].

Opioids: Fentanyl and meperidine bind to opioid receptors in the central and peripheral nervous systems, acting as potent analgesics and sedatives. Fentanyl, has a faster onset, shorter duration, and reduced nausea compared to meperidine, making it preferred for GI procedures[7,12]. Respiratory depression, bradycardia, and hypotension are primary adverse effects of fentanyl, which can be reversed with naloxone[13].

Propofol: Propofol outperforms other sedatives in terms of procedural success, patient satisfaction, and recovery[14,15]. It’s a highly lipophilic compound with rapid onset and short half-life. A meta-analysis of 36 randomized trials showed that propofol with midazolam and fentanyl resulted in deeper sedation, higher satisfaction, and faster recovery[6]. Propofol’s safety concerns are low, with complication rates comparable to or lower than benzodiazepines combined with opioids[16]. However, it has a narrow therapeutic window, lacks an antidote, and may cause cardiorespiratory complications in certain populations, like the elderly.

Remimazolam: Remimazolam, a short-acting benzodiazepine, was recently approved by the Food and Drug Administration in July 2020. A study by Rex et al[17] demonstrated the superiority of remimazolam over midazolam in procedure success rates, with a significantly higher success rate of 13.3% compared to midazolam (P < 0.01). Remimazolam exhibited comparable procedure success rates for upper endoscopies compared to propofol, but higher concentrations led to adverse effects such as nausea, vertigo, and prolonged sedation recovery time[18]. Another study by Liu et al[19] indicated that the remimazolam group demonstrated a superior safety profile compared to propofol in terms of hypotension, vasoactive drug use, bradycardia, respiratory depression, and overall adverse events. Consequently, remimazolam appears promising, but further research is necessary to establish its efficacy and safety.

RETHINKING SEDATION IN GI ENDOSCOPY

All patients should be classified according to the ASA classification[20], and risk factors including cardiovascular risks, obesity, obstructive sleep apnea, alcohol or substance abuse, adverse reactions to sedative drugs, and the type of procedure should be determined. All these factors are crucial in determining the optimal mode of sedation.

Blood pressure, heart rate, and pulse oximetry should be monitored during the procedure according to available guidelines, along with visual assessment of ventilatory activity, level of consciousness, and discomfort[21]. ECG monitoring is indicated in patients with significant cardiovascular disease or dysrhythmia, significant pulmonary disease, or in the elderly during moderate sedation[22].

Limitations imposed by the small patient sample notwithstanding, the findings from the current investigation led by Cohen and Kim[23] cast interest on the safety and efficacy of a practice using midazolam alone to sedate adults during routine diagnostic or therapeutic endoscopy. Monitored anesthesia care is common but faces staffing shortages and high costs. Nurse-administered propofol sedation (NAPS) is a cost-effective alternative. A global review of 646080 NAPS procedures reported only 11 emergent endotracheal intubations, no permanent neurological injuries, and 4 fatalities; only 0.1% of patients needed transient mask ventilation[24]. Most GI guidelines allow NAPS for low-risk GI procedures in ASA levels I and II patients with adequate training and certification.

However, increasing dependence on anesthesia personnel in the delivery of propofol sedation has required an increase in service cost, especially in day-care practice. Nonetheless, multiple contemporary practices feature widespread use of midazolam and fentanyl. The novelty of this study was the attempt to answer a common, unanswered question in the medical community: (1) Is single-agent midazolam ever appropriate; and (2) Is midazolam coupled with fentanyl still the right combination.

One of the most remarkable results of Cohen and Kim’s research is that the levels of patient satisfaction are, to a surprisingly high degree, the same between the midazolam alone and the midazolam and fentanyl groups[23]. The authors measured each with the Procedural Sedation Assessment Survey and found no clinically important difference in pain or desired sedation states. With no difference in comfort or efficacy, it appears that midazolam alone could offer a clinically useful alternative, especially in low-risk patients.

The significance of these findings is enormous. Although fentanyl is a highly effective drug for pain management, it has side effects such as nausea, respiratory depression, and hemodynamic instability. Healthcare providers could potentially improve patient safety while preserving comfort by reducing or avoiding fentanyl. In fact, reports suggest that some patients exhibit nausea in response to fentanyl and eliminating such a side effect might render the recovery profile more desirable. Furthermore, with the increase in the number of ambulatory cases, it becomes important to acknowledge the costs of sedation. The use of midazolam alone could potentially have positive cost implications with regards to drug administration and monitoring. Nonetheless, the single-blinded nature of the study and having only one endoscopist perform all procedures are potential important limitations for the generalizability of the findings. The possibility of longer cecal intubation times in the midazolam-only group associated with a higher total dose of midazolam should receive more attention. It indicates that with care and method extra-pharmacological intervention may replace further pharmacological treatment. In the light of the above findings one cannot but compare to the recent large trial published earlier this year. Xie et al[25] presented a retrospective analysis of more than 56000 cases undergoing endoscopy, when they compared several protocols of sedation. They concluded that although combination midazolam and fentanyl showed lower rates of adverse events, it resulted in much longer in-hospital recovery period and stay time compared to all other groups including those who received general anesthesia.

Though the present study does not provide clear answers, it still suggests a cornerstone for future investigation into sedation practice in the setting of GI endoscopy and the relative merits of midazolam as an agent of sedation alone.

CONCLUSION

To date there seems to be no consensus on endoscopic sedation. Protocols still vary between various institutions and various countries. Moderate sedation, whether achieved with a combination of midazolam and opioids or midazolam alone is still considered effective and safe. However, in developed countries, with the advances and complexity of GI procedures, there is a growing trend toward deeper sedation using propofol. Another debatable issue remains whether propofol administration mandates the presence of an anesthesiologist. Emerging drugs such as remimazolam show promise in this field. The key is to balance efficacy and safety with precision. It depends on multiple factors, primarily patient characteristics, as well as the type and duration of the procedure. Ongoing research and future trends need to focus on newer molecules providing an equilibrium between safety and efficacy in sedation. Further efforts should be invested in standardizing the multiple guidelines available and unifying the protocols for better quality of medical care. A shift in practice, if supported by additional research, could redefine sedation protocols, enhance patient safety, and potentially lead to significant cost savings in outpatient settings. As the field continues to evolve, it's critical that we remain open to innovation backed by scientific inquiry, paving the way for better practices in patient care.