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Abstract

Pulse oximetry is a critical component of patient monitoring to ensure adequate oxygenation in the perioperative period. However, its use remains limited in low- and middle-income countries due to device scarcity, limited funding, and lack of training. This prospective observational study describes the incidence of early postoperative hypoxemia (EPH) with newly implemented portable pulse oximetry and associated factors that impact postoperative management at the Hospital Nacional de Coatepeque (HNC), a primary referral public hospital in Guatemala. Semi-structured interviews were conducted with perioperative medical staff to explore perspectives regarding postoperative monitoring and patient safety in a resource-limited setting. One hundred patients were included, of which 10% experienced EPH. Patient age was significantly associated with EPH. The average duration in the recovery area of 14 minutes, with a lack of subsequent monitoring, was a primary concern of the 14 interviewed medical personnel. The greatest perceived needs include enhanced monitoring, increased staffing, and a dedicated post-anesthesia care unit. Pulse oximetry is essential to detect previously unrecognized EPH. Improved postoperative monitoring and increased recovery time and staffing are priorities to enhance patient safety at public hospitals in Guatemala.

Introduction

Monitoring tissue oxygen saturation through pulse oximetry has become an international standard of care, providing valuable information about a patient’s clinical status to ensure adequate oxygenation in the perioperative period [1]. Yet, pulse oximetry remains underutilized in some areas in low- and middle-income countries (LMICs) due to barriers such as device scarcity, insufficient funding, and lack of training. Research has demonstrated that the implementation of portable pulse oximetry is a cost-effective intervention in resource-limited settings that enables early detection of hypoxia before irreversible damage occurs [2-5].

In recent years, large-scale initiatives have expanded the availability and broader use of pulse oximetry in many LMICs, leading to significant improvements in perioperative care and patient safety [2,3,6]. However, most of these initiatives have taken place in Africa and Southeast Asia. There are no documented studies of implementing portable pulse oximetry in first-referral hospitals in Guatemala. Due to limited capacity and infrastructure, data on complications arising from a lack of monitoring is scarce and not widely available.

In Guatemala, 88% of health care is provided through the public health system. Limitations in funding, equipment, and workforce can impact care delivery in public hospitals, especially in more remote regions of the country. For example, one survey of national capacity reported that only 70% of district hospitals had a consistent supply of oxygen, and only 50% of national hospitals reported always or almost always having pulse oximeters [7]. In southwestern Guatemala, the Hospital Nacional de Coatepeque (HNC) is a first-referral, public hospital that provides care to high-risk surrounding rural communities in Coatepeque, Quetzaltenango District, Guatemala [8]. We performed a needs assessment at the HNC in 2023 which revealed a lack of postoperative physiologic monitoring and a designated post-anesthesia care unit (PACU). After surgery, patients at HNC wait in a holding area until nursing staff become available to transfer them to their respective medical units.

Through the Safe Surgery Initiative of the non-profit AmeriCares organization, two portable pulse oximeters (CMI Health Handheld Pulse Oximeter PC66-H, CMI Health, Alpharetta, GA) were provided as donations to the hospital for monitoring patients during the immediate post-surgical period. These devices are rechargeable and HNC has reliable access to power for recharging. Utilizing newly implemented pulse oximetry, we investigate patient and health system factors that impact postoperative patient care and outcomes in a resource-limited hospital in Guatemala. Through pulse oximetry implementation, we expect an increased detection of hypoxemic events and the associated risk factors. Additionally, we explore the perceptions of hospital staff concerning the health system and process factors that impact postoperative care and safety.

Materials & Methods

This prospective observational study describes the incidence of early postoperative hypoxemia (EPH) and the management of patients in the immediate post-surgical setting at the HNC. Hypoxemic events, defined as periods with oxygen saturation (SpO₂) less than 90%, were previously undetectable due to a lack of essential resources, including a designated PACU and pulse oximeter monitoring. This study was approved by the Colorado Multiple Institutional Review Board and local K’Awil ethics committee and adheres to the applicable Enhancing the QUAlity and Transparency Of health Research (EQUATOR) Network guidelines for The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) [9].

Data regarding the early postoperative course and oxygen saturation levels were collected from a convenience sample of patients who presented after surgery at the HNC during four one-week periods from May to August 2024. The consent process was conducted in Spanish by language-certified research team members or the local care team, and informed consent was obtained from patients preoperatively. Patients were notified of their right to refuse participation without any consequences to their medical care. All patients were provided the opportunity to ask questions during the initial consent and at any point to ensure full understanding. In illiterate patients who were unable to sign, hospital protocols were followed with fingerprint stamps, and consent materials were verbally presented to patients. Exclusion criteria included inability to consent, refusal, or age less than one year. All other patients who consented to participate were enrolled in the study. Research team members who were not directly involved in the perioperative care observed the patients in the postoperative holding area and recorded the occurrence and characteristics of EPH, postoperative management, surgery and anesthesia type, and basic patient information (age, gender, body mass index [BMI], American Society of Anesthesiologists [ASA] score). Information was stored without direct identifiers in a secure online database that was only accessible to the research team.

Additionally, semi-structured interviews were performed in Spanish with perioperative HNC staff who consented to participate. These interviews examined the providers’ perceptions of patient safety needs and concerns in the perioperative setting. Due to a lack of existing validated surveys that addressed our study objectives, we designed a brief interview guide that consisted of two primary questions: 1. What are the greatest perioperative needs in the hospital? 2. What are your greatest concerns for patient safety? After prompting the questions, interviewees were given the opportunity to freely discuss any additional topics. All interviews lasted between 2-8 minutes and were audio-recorded using a secure, encrypted mobile application. Participants were assured that responses would not affect employment, and only their profession was recorded.

Descriptive statistics were calculated and presented as frequencies with percentages, means, and standard deviations (SD). A multiple logistic regression was used to test for a relationship of experiencing a hypoxemic event with relevant clinical factors using Stata statistical software (StataCorp LLC, College Station, TX, 2023). A Bonferroni correction was performed to reduce the risk with multiple testing, and a modified statistical significance level of p <0.01 was considered significant. The sample size was based on the number of patients available during the study period, due to the severe local staffing constraints and the availability of research team support. Interview participants were selected from each relevant specialty, and we aimed to recruit at least 12 individuals to reach saturation of relevant themes. Audio recordings were reviewed, and primary codes were developed for each interview by two research team members. Coded data was analyzed for major themes between profession types and then counted and displayed as frequencies among respondents.

Results

A total of 100 patients were included, 41% of whom were female (Table 1). Ten (10%) patients had at least one recorded episode of hypoxemia during the immediate postoperative period, with the lowest recorded oxygen saturation of 86% (Table 2). The longest hypoxic event lasted 90 seconds, with stimulation as the primary intervention. Only one patient during the study received supplemental oxygen therapy in the postoperative area.

Age was significantly associated with EPH (p=0.004), with an odds ratio of 1.11 (99% confidence interval: 1.03431, 1.193091). The average duration in the immediate postoperative area before transfer to the floor was 14 (SD 8.6) minutes. Of note, there was no staff present during the entirety of the recovery period to monitor patients while awaiting transfer to their respective hospital units.

Interviews were performed with 14 HNC medical personnel, including anesthesiologists (n=5), surgeons (n=2), perioperative nurses (n=4), and surgical unit nurses (n=3). Interviews with medical providers revealed widespread concerns of inadequate postoperative monitoring during recovery and after transfer to the units due to the short duration in the recovery area, with primary safety concerns being hemodynamic instability, respiratory complications, and mental status due to residual anesthetics (Figure 1). The greatest needs identified were the establishment of a designated PACU, and additional nursing staff and physiologic monitoring (Figure 2).

Discussion

Pulse oximetry enabled the detection of hypoxemic events at HNC that were previously unrecognizable, providing valuable information regarding clinical status during the high-risk period immediately after surgery. In this population, events were typically of short duration and resolved primarily with stimulation, without any significant patient complications. However, delayed identification and lack of early intervention can lead to severe complications and preventable morbidity and mortality. Respiratory complications, commonly due to airway obstruction, hypoventilation, atelectasis, bronchospasm, and acute respiratory failure, are leading causes of increased hospital stay and healthcare costs following major surgeries [10]. Thus, the use of pulse oximetry is recommended in the postoperative period, particularly in those at an increased risk for respiratory complications [11,12]. Despite worldwide efforts to promote the expansion of pulse oximetry, there is a discrepancy between the actual and the expected use of pulse oximeters in LMIC settings, though this improved with the implementation of donated devices [6]. This report demonstrates the ongoing need for assistance in supplying portable monitors to resource-limited public hospitals in Guatemala.

In this cohort of postoperative patients who were not placed on supplemental oxygen, 10% of patients experienced a desaturation event. This is consistent with prior studies of oximetry in LMICs who have reported an incidence of EPH ranging from 4% to 24% [5,13,14]. The high rate of orthopedic and trauma surgeries and low rate of general anesthesia compared to regional techniques reflect the standard practices in this hospital. Regional anesthesia is often preferentially used in many LMIC settings for resource optimization and patient safety, where there may be lower rates of hypoxemia compared to high-income countries, where general anesthesia is more common [15]. Patients who receive general anesthesia have been reported to have an eight times greater chance of developing hypoxemia than those who receive regional anesthesia. Factors that have been shown to contribute to postoperative hypoxia include type of anesthesia, type of surgery, age, severe pain, history of obstructive sleep apnea, and duration of anesthesia [13,14]. In this patient cohort, a statistically significant association was only observed with age, though the incidence of desaturation was nearly doubled in patients who received general anesthesia. The small sample size may contribute to a lack of statistical significance observed with other factors, such as anesthesia type, in this population. Age has been associated with EPH in prior studies in LMICs [13,14]. Advanced age can result in a decline in pulmonary function and increased sensitivity to pharmacologic agents and has been shown to be an independent risk factor for postoperative pulmonary complications [16,17]. In this hospital setting with limited resources, the identification of higher-risk patients can be useful to allocate resources, such as oxygen or continuous physiologic monitoring, or modify care plans to prevent postoperative complications.

The clinical relevance of hypoxemic events can be context-dependent. Though oxygen desaturations of short duration are often tolerated in healthy patients without significant organ damage, even mild hypoxemia in critically ill patients can be an independent risk factor for increased mortality [18]. Brief episodes of hypoxemia can be associated with worse long-term outcomes and significant physiological responses such as respiratory changes, increased heart rate, and vasoconstriction, which can exacerbate cardiovascular risks [19,20]. These physiologic perturbations may also lead to cognitive impairment, which could impact patient management and resource allocation in settings such as HNC with limited patient supervision. Further analysis of the impact of hypoxemia on long-term clinical outcomes in this patient population is outside of the scope of this study but is warranted to better understand the clinical implications of EPH in resource-limited settings.

In addition to cost and device availability, human factors, such as lack of expertise and training, have been identified as barriers to implementing pulse oximetry in LMICs [21]. Over the course of the study, local staff were trained on the new devices and provided with printed manuals and instructions for use and troubleshooting. Although care was deferred to the local team and their practice was observed, there were collaborative discussions about patient management and protocols for staff related to postoperative observation and response to device alerts, in accordance with hospital policies and available resources. Ongoing education and training are essential for the sustainable integration of new technology and practices in diverse health systems [22]. Ensuring a reliable power source for device operation is also an important factor in considering the feasibility of implementation. The devices in this study are rechargeable and there are no concerns about access to a reliable power supply for recharging. Advancements in portable monitoring technology, such as pulse oximetry and capnography, have facilitated global application and use, and the ongoing promotion of these devices should be prioritized.

A significant observation of this study was the short duration in the recovery area and the lack of direct supervision and patient monitoring after surgery. The limited average time of only 14 minutes in the immediate postoperative area, with a short duration of pulse oximetry monitoring and rapid transfer to the wards, where no monitoring occurs, could contribute to a lower number of EPH and result in missed events that could occur during prolonged recovery from anesthesia. In contrast, the length of stay for PACU monitoring in a high-income setting can typically range from 1 to 5 hours [23]. Although one study in Ethiopia observed the majority of hypoxemic events in the first 10 minutes after surgery, hypoxemia still occurred during the first 30 minutes of follow-up in the PACU [24]. This concern was expressed by nearly all HNC team members, who acknowledge the lack of monitoring in the wards, where there are high patient-to-nurse staffing ratios, limited training, and a lack of equipment or oxygen supplies. These challenges highlight the importance of a designated PACU for safe postoperative recovery. The lack of a PACU has been identified in nearly 20% of public hospitals in Guatemala and has also been reported in other LMICs [7,25-27]. As expressed by the HNC providers, a designated PACU would improve safety by prolonged physiologic monitoring of higher-risk postoperative patients by trained personnel with improved staffing ratios and proximity to the operating room and anesthesia team and reduce the burden on the hospital units’ nursing staff. Timely nursing care can reduce complications including hypoxemia, hypotension, pain, and nausea, but requires adequate staffing, training, and protocols [28]. Based on the reviews of the literature, investment in increased perioperative nurse staffing and a designated PACU could potentially be a cost-effective strategy to improve care quality and patient outcomes in this resource-limited setting [29].

Limitations

A limitation of this study is the small sample size from a single center. While the sample size of 100 subjects enabled the detection of a statistically significant association with EPH and age in this cohort, the ability to detect small differences and associations with other risk factors may have been limited, especially when correcting for multiple testing. The use of convenience sampling could limit generalizability to other centers but was performed to analyze the true surgical population in this hospital setting, though temporal trends in surgical procedures and patient demographics could exist. Additionally, the brief monitoring period may have prevented additional findings of EPH, which could have been captured with prolonged postoperative monitoring. As previously discussed, this is an area of active concern that warrants further investigation.

Conclusions

Portable pulse oximetry is an effective tool for detecting previously unrecognized hypoxemia in postoperative patients in resource-limited settings. Despite widespread efforts to expand the use of portable pulse oximetry, this report demonstrates the ongoing need for the implementation of this essential technology in resource-limited settings. The patient and system risk factors identified in this study can inform future strategies to improve postoperative patient safety in public hospitals in Guatemala. Extended patient monitoring and the establishment of a dedicated PACU with adequate staffing and equipment are necessary to avoid preventable patient complications and ensure optimal patient outcomes after surgery.

References

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Abstract

The emergence from general anesthesia is currently difficult to predict and may be accompanied by respiratory complications. Switching all hypnotic drugs to remimazolam at the end of the operation and antagonizing it with flumazenil might lead to a rapid, smooth, and safe patient awakening, potentially increasing operating theater efficiency and reducing costs. In this case series of five patients, anesthesia with a combination of remimazolam, propofol, and sevoflurane was transitioned to remimazolam at 0.9-1.0 mg/kg/h as the sole hypnotic agent near the end of the operation. Subsequently, remimazolam was antagonized with 0.5 mg flumazenil. This approach resulted in a rapid, predictable, and smooth emergence and recovery, free from excitation or hemodynamic and respiratory disturbances. Additionally, postoperative opioid requirements were minimal, and no anti-emetic medication was necessary. The authors conclude that the “switch and antagonize” concept is feasible and promising, warranting further evaluation and refinement in the near future.

Introduction

Ending anesthesia after an operation is typically achieved by discontinuing all anesthetic agents and allowing them to wear off until the patient is deemed sufficiently awake and/or spontaneously breathing for extubation. Predicting the time required for anesthetic agents to wear off adequately can be challenging, potentially leading to prolonged emergence from anesthesia and delayed extubation, thereby occupying the costly resources of an operating theater and staff. Furthermore, during the transitional phase between full general anesthesia and full wakefulness, the patient is at risk of respiratory complications such as laryngospasm, bronchospasm, and respiratory depression, which may result in serious injury to the patient [1].

In contrast to the significant emphasis placed on preventing complications during intubation, the potential risks associated with emergence and post-extubation are often underestimated [2]. Moreover, waiting for all anesthetic agents to wear off completely can prolong the patient’s stay in the recovery room and is associated with more post-anesthetic recovery issues, including hypotension, respiratory depression, postoperative nausea and vomiting (PONV), and patient discomfort, all of which are caused by the residual effects of the anesthetic agents used.

With the introduction of the short-acting benzodiazepine remimazolam for general anesthesia, it has become possible to antagonize its effects with flumazenil immediately after the operation is completed. Using remimazolam as the sole hypnotic for maintaining general anesthesia may offer advantages, such as reduced intraoperative hypotension [3], but it also has disadvantages, including less suppression of intraoperative movements compared to other hypnotics [4,5], the risk of residual sedation in some patients [6], a higher likelihood of postoperative nausea [7], and a poorer overall quality of recovery when used as a single sedative [6].

Therefore, the use of remimazolam for anesthesia maintenance may require further optimization before being incorporated into standard anesthesia regimens. This could involve combining it with the favorable properties of propofol (anti-emetic effects) and volatile anesthetics (suppression of spinal reflexes). Employing a standard maintenance strategy that combines propofol, a volatile anesthetic, and remimazolam also has the benefit of a rapid emergence time, as each hypnotic can be administered at a low dose and cleared through different mechanisms. Another potential approach is to switch all hypnotic drugs to remimazolam toward the end of the operation, offering the advantage of its antagonism with flumazenil.

Recently, a case report has described the use of remimazolam after general anesthesia with sevoflurane, a volatile anesthetic, followed by flumazenil administration [8]. In this report, the patient was extubated under deep anesthesia, and flumazenil was administered after extubation. Additionally, Jeon et al. [9] reported the transition from propofol to remimazolam one hour before the end of surgery, followed by flumazenil reversal in 54 adults with mental disabilities undergoing dental treatment under general anesthesia.

A systematic review and meta-analysis has demonstrated that the combination of remimazolam and flumazenil accelerates recovery from general anesthesia and reduces the risk of respiratory depression compared to the commonly used hypnotic drug propofol [10]. Switching all hypnotic drugs to remimazolam at the end of surgery, followed by antagonization with flumazenil, may facilitate a fast and smooth awakening of the patient. Furthermore, this anesthetic regimen could enhance patient and physician satisfaction, improve patient safety, and increase operating theatre efficiency, thereby reducing costs. This technique is anticipated to be increasingly adopted in daily clinical practice. Here, we report our experience transitioning to remimazolam followed by flumazenil in five orthopedic patients undergoing total hip arthroplasty.

Case Presentation

The Medical Research Ethics Committee of East Netherlands approved this retrospective case series, which used only data already stored in the patients’ electronic files without further interventions or measurements (approval number: 2024-17800). Only data from patients who explicitly consented to the anonymous use of all their clinical data for retrospective research were included, as documented in their electronic patient records. The Committee waived the requirement for additional patient consent.

Patient information

We retrospectively evaluated adult patients aged <70 years, with an American Society of Anesthesiologists (ASA) classification <3 and body mass index (BMI) <30, who were scheduled for total hip prosthesis surgery under general anesthesia with remimazolam and received its antagonist, flumazenil, at the end of the surgery. Using these criteria, a search of the electronic patient record system identified five patients. Demographic characteristics are presented in Table 1.

Five adult patients (two males and three females) with a mean age of 58 ± 14.4 years were included. Four patients were classified as ASA physical status class II and one as ASA class III. All patients had normal BMI (25 ± 1.0).

Anesthetic regime and switching and antagonizing

Next to the standard non-invasive monitoring, including electrocardiography, oxygen saturation, and non-invasive blood pressure, a frontal electroencephalogram (EEG) was attached to the patient’s forehead to measure the bispectral index (BIS). A neuromuscular monitor was also attached to the patient’s wrist to assess the degree of neuromuscular block.

During induction, infusion pumps delivering propofol (approximately 2 mg/kg/h) and remimazolam (approximately 0.3 mg/kg/h) were initiated and administered through the same intravenous line. Subsequently, a bolus of 15-20 µg sufentanil and remimazolam (0.20-0.21 mg/kg) were administered. All doses were calculated based on actual body weight. The intraoperative medications administered, including time frames for switching and antagonizing, are summarized in Table 2.

When the patient was asleep, a single dose of 35-40 mg of rocuronium was administered to induce muscle relaxation for the placement of the endotracheal tube. Sevoflurane was added at approximately end-tidal 0.4 MAC, age-corrected. This MAC value was displayed directly on the monitor of the GE Datex Ohmeda Advance anesthesia machine. The age-corrected MAC for sevoflurane was internally calculated using the following formula:

This combination of remimazolam, propofol, and sevoflurane has recently been reported as triple anesthesia [11] and is commonly used in our department. After induction, 10 mg of piritramide was added in four patients, and 20 mg of piritramide was added in one patient as a long-acting opioid. No other opioids were administered after the induction of anesthesia.

As is standard in our department for orthopedic surgery, patients received premedication with 1,000 mg of paracetamol and 150 mg of pregabalin. Intraoperatively, a multimodal analgesic concept was employed, consisting of 40 mg of parecoxib, 8 mg of dexamethasone, a 5-10 mg bolus of esketamine followed by a continuous infusion at 5-10 mg/h, and a 40 mg/kg bolus of magnesium chloride followed by a continuous infusion at 500 mg/h. Approximately 45 minutes before the end of surgery, esketamine and magnesium chloride were discontinued. When the end of surgery was anticipated within 20-25 minutes, propofol and sevoflurane were stopped, and remimazolam was increased to 0.9-1.0 mg/kg/h (Table 2). After confirming the absence of residual neuromuscular blockade, spontaneous breathing was encouraged. After the operation, the infusion of remimazolam was stopped, and 0.5 mg of flumazenil was administered 1-2 minutes later. Once the patients opened their eyes, the endotracheal tube was removed.

Clinical parameters and time frames after antagonizing

All patients remained hemodynamically stable throughout the procedure. No significant alterations in blood pressure were observed after switching to remimazolam as a mono-anesthetic. The time from flumazenil administration to extubation was two minutes in three patients and one minute in two. Additionally, no desaturation occurred in any of the patients. BIS values increased from 67.2 ± 9 to 83.3 ± 6.8 following the administration of flumazenil (Figure 1).

No signs of excitation were observed in any of the patients, and no sudden changes in vital parameters occurred after antagonization. No patient movements or coughing were observed during switching or antagonization. Patients emerged calmly from general anesthesia and were quickly transferred to the recovery room. Overall, no adverse events occurred.

Clinical course in the recovery room and normal ward

The administration of opioids in the recovery room and normal ward was minimal, as presented in Table 2. In the recovery room, three patients received a dose of 5 mg piritramide, while no piritramide was administered to two patients. On the ward, one patient with an allergy to oxycodone received a single sublingual dose of 0.2 mg buprenorphine. Among the other four patients, one received a single 5 mg dose of oxycodone during the first 24 hours postoperatively, while the remaining three patients did not receive any additional opioids on the ward. No anti-emetic drugs were required during the entire 24-hour postoperative period.

Discussion

In this case series, a concept of “switch and antagonize” was used, which involved switching from a combination of remimazolam, propofol, and sevoflurane as hypnotic maintenance of anesthesia to remimazolam as the sole hypnotic agent near the end of the operation. Combined with flumazenil, this approach resulted in a rapid, predictable, and smooth recovery free from excitation or hemodynamic and respiratory disturbances. It demonstrates the feasibility of achieving controlled emergence from general anesthesia in humans through specific antidotes.

In 2023, Araki and Inoue described switching to remimazolam after anesthesia with sevoflurane, followed by flumazenil for the deep extubation of a patient with bronchial asthma [8]. While they administered flumazenil after deep extubation, Jeon et al. [9] reported an approach more similar to ours, involving the administration of flumazenil prior to extubation. They described converting from propofol to remimazolam with flumazenil reversal in adults with mental disabilities undergoing dental treatment one hour before the end of surgery [10]. To our knowledge, there are no other reports on “switch and antagonize.”

Several interesting questions remain. When should the switch occur? The timing of the switch should be long enough to sufficiently decrease the residual amounts of sevoflurane and/or propofol. However, a switch as close as possible to the end of surgery would be advantageous from a practical standpoint. Our data suggest that the one hour prior to the end of surgery, as used in the study by Jeon et al., may not be necessary. Even in the presence of long-acting opioids, a time point 20-30 minutes before the end of surgery might be sufficient. Nevertheless, this should be further investigated with larger sample sizes. It is also unclear whether an even shorter time interval could be feasible.

Certain operations, such as hip arthroplasty, allow for a better estimation of the remaining procedure time compared to others, such as intraoral procedures (Jeon et al. reported a relatively high standard deviation for the duration of remimazolam infusion at 64.7 ± 25 minutes) or laparoscopic surgery. This variability should be considered when planning the timing of the switch for specific procedures.

Another anesthetic regimen that could be interesting to investigate in larger randomized trials is propofol, remimazolam, and sevoflurane. At the end of the surgery, hypercapnic hyperventilation could be employed to rapidly eliminate sevoflurane and propofol, along with flumazenil, for the antagonism of remimazolam. This strategy has shown promise in several small studies [12-14].

How to switch? Araki and Inoue repeated the induction dose of remimazolam while switching. However, we do not believe this is necessary. Even after stopping propofol and/or sevoflurane, the plasma levels require some time to decrease, which might correspond to the time needed for the plasma levels of remimazolam to increase during initiation or escalation of remimazolam infusion. This aligns with the study by Jeon et al., who also did not administer a bolus of remimazolam during switching.

Araki and Inoue used a remimazolam dose of 0.8 mg/kg/h from the completion of the laparoscopic procedure until skin closure. This is comparable to our dosing regimen of 0.9 mg/kg/h after switching. Jeon et al. reported a remimazolam dose of 1-2 mg/kg/h, adjusted based on a processed EEG value after switching.

How much flumazenil is needed to antagonize remimazolam? Many studies on remimazolam and flumazenil, such as Toyota et al. [15], used a standard dose of 0.5 mg of flumazenil. Jeon et al. and our study also used the same dose of 0.5 mg of flumazenil. In contrast, Araki and Inoue used a dose of 0.9 mg of flumazenil. A titration approach, such as administering 0.2 mg of flumazenil followed by repeated doses of 0.1 mg every minute up to 1 mg until arousal [6], is also an option. However, as fast extubation without a prolonged “twilight zone” between full general anesthesia and complete wakefulness is preferred, starting with a higher standard dose might be more advantageous. Greater pharmacodynamic-pharmacokinetic insight into the relationship between remimazolam plasma levels and the required flumazenil dose could provide clinically important information in the future.

Some potentially negative clinical aspects of the remimazolam-flumazenil setting should be considered, such as extubation recall, PONV, and postoperative pain. Sato et al. concluded in a study of 163 patients that the incidence of extubation recall after remimazolam anesthesia with flumazenil antagonism during emergence did not significantly differ from that after propofol anesthesia [16]. Wei et al. reported that flumazenil antagonism of remimazolam might increase the incidence of PONV [7]. Although we did not specifically investigate PONV in our patients, the electronic patient records did not mention PONV in any of the five patients, and no antiemetic drugs were administered in the recovery room or on the ward. Interestingly, our extensive multimodal analgesic concept resulted in very low postoperative opioid use.

In rare cases (0.1-1%), the administration of flumazenil may lead to fear and palpitations. However, these side effects are transient and are most prominent when flumazenil is administered to awake patients rather than when used in asleep patients, as was the case in the current study design.

Due to the small sample size and retrospective study design, no strong conclusions can be drawn from our data. Furthermore, rather than focusing on individual variables, future studies should investigate whether our approach benefits overall recovery quality and the incidence of complications. More research involving larger groups of patients is warranted to verify whether the “switching and antagonizing” approach results in reduced and predictable extubation times and a more efficient workflow and reduces the risk of airway complications during and after extubation. This approach may be of particular interest to patients at increased risk of airway complications, such as those with difficult airways, bronchial hyperreactivity, or an elevated risk of aspiration.

Conclusions

Our case series demonstrates that the “switch and antagonize” concept is feasible and resulted in a rapid and smooth emergence and recovery in five patients, free from excitation or hemodynamic and respiratory disturbances. This was achieved by switching from combining remimazolam, propofol, and sevoflurane to remimazolam as the sole hypnotic agent, combined with flumazenil. Additionally, postoperative opioid use was minimal, and there was no need for antiemetic medication. Whether the “switch and antagonize” protocol could shorten the time to extubation and improve recovery predictability and efficiency should be investigated further. Moreover, cost-effectiveness and further evaluation and fine-tuning of this concept are needed, with particular emphasis on its application in patients with risk factors such as difficult airways or an increased risk of aspiration. It appears promising for future clinical use, especially for vulnerable patient groups, but larger (case-control) studies are essential to fully understand this approach’s potential.

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