Ketamine administration for rigid bronchoscopy in adult: literary review and the operator perception

Introduction

Central airway obstruction (CAO) is a potentially presentation of lung cancer (1). It may be a life-threatening condition that requires urgent rigid bronchoscopy (RB) treatment (2). Anesthetic management of such patients is challenging as performing RB demands to keep reliably deep anesthesia and to ensure airway patency and lung ventilation/oxygenation. Indeed, airway patency may be lost with use of neuromuscular blocking (NMB) drugs—as they abolish muscle tone—and desaturation could occur due to respiratory depression linked to administration of some medications (e.g., propofol and opioids). On the other hand, achieving a deep anesthesia is necessary to achieve compliance by the patient and avoid remarkable discomfort for the surgeon/interventional pulmonologist. Furthermore, RB alternates periods of high and low stimulation on the airways. So the ideal anesthetic should reliably maintain a patient unconscious and immobile and guarantee hemodynamic and respiratory stability (3). Volatile anesthetics administration is complicated by the type of intervention where moments of apnea are possible and by the category of patients that are often burdened from relevant respiratory comorbidities. In this scenario some authors suggested the use of total intravenous anesthesia (TIVA) for RB procedure because intravenous anesthetics are more rapidly titrated and able to meet fluctuating necessities. Remifentanil and propofol remain the mainstay drugs for TIVA, due to their strong and short-acting properties (4). Nevertheless, the combination of an opioid with propofol is associated with several side effects, such as respiratory depression, postoperative nausea and vomiting, propofol-induced hypotension and opioid-induced bradycardia. Only few authors focused on the possible benefit of ketamine and there is growing interest regarding its use for endobronchial procedures (5). We present this article in accordance with the Narrative Review reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1715/rc).

Methods

First, we described main features about ketamine effects. Then, we collected the main reports about ketamine usage in adult thoracic endoscopy (Table 1 summarizes our search strategy) and introduced our initial experience with ketamine usage in RB. After, we briefly reported the possible ventilation strategies and our operators’ feelings about the eventual comfort experienced during the procedures.

Pharmacological issues

Ketamine is an N-methyl-o-aspartate receptor antagonist that induces a dissociative state where sensory input normally perceived by the patient is blocked so that it does not reach consciousness. Ketamine is particularly suitable for endobronchial procedures because it has bronchodilating properties and does not depress respiration (6). Ketamine exerts also sympathomimetic effects which may prevent from hypotension events. On the other hand it is necessary to pay attention when dealing with patients who have poor control of blood pressure values at home. Ketamine is also burdened by possible emergence reactions but mainly when it is administered as the sole anesthetic agent (7).

Flexible bronchoscopic experiences with ketamine

Ketamine is usually employed in pediatric surgical and endoscopic context but there are also some reports about thoracic endoscopy—mainly flexible bronchoscopy (FB)—for adult patients (summary available in Table 2). Palle Toft and Ulle Romer reported a double-blind prospective trial including 50 patients undergoing laryngoscopy, bronchoscopy and mediastinoscopy. They compared midazolam with diazepam using TIVA based on ketamine-benzodiazepine-fentanyl infusion. The midazolam-ketamine group had a significantly shorter time to more complete recovery and significantly lower frequency of emergence reactions (8). Hwang et al. reported a randomized, double-blind study to compare ketamine and alfentanil combined with propofol for patient-controlled sedation during FB (9). They included 280 adult patients undergoing elective procedures with lung cancer as main indication (55%). Ketamine showed better patient satisfaction and amnesia than alfentanil. Sazak et al. analyzed retrospectively perianesthetic data from 571 patients undergoing transbronchial needle aspiration using endobronchial ultrasonography (EBUS-TBNA). These procedures were performed with different anesthetic drugs combination: propofol-midazolam, propofol-ketamine, propofol-ketamine-midazolam or propofol alone (10). Independent from the sedative agent, deep sedation was safe with high patient satisfaction reported. Ketamine combined with propofol or midazolam required lower doses usage. However, there was higher incidence of increased blood pressure in ketamine administration groups. Dal et al. compared 60 patients undergoing EBUS-TBNA that were randomly divided in two groups: ketamine-midazolam and ketamine-propofol combinations (11). They recorded, blood pressure, heart rate, peripheral oxygen saturation, respiratory rate, Ramsay Sedation Score (RSS) and severity of cough prior to and after the drugs administration. They concluded that both sedative combinations were similarly effective and safe. Fruchter et al. evaluated the safety and efficacy of sedation comparing ketamine-propofol-midazolam with the fentanyl-propofol-midazolam regimen (12). Eighty patients undergoing FB were randomly divided in two groups. Vital signs, sedation-related complications and interventions to maintain respiratory and hemodynamic stability were assessed. No significant differences were noted between the two groups. Ulutas et al. designed a prospective, randomized double-blinded trial where 64 patients undergoing FB were included. There were two different drug regimens administered by the anesthesiologist: ketamine/propofol (ketofol) and propofol alone. Vital signs, Visual Analogue Scale (VAS) and RSS were recorded (13). Ketofol resulted to be better with statistical significance than propofol alone in vital signs control and procedure tolerability according to VAS. On the other hand, the groups were generally cooperative and calm during the procedure and no statistically significant differences were detected according to RSS. Other authors described the effect of esketamine which is the s-enantiomer of ketamine racemate, that shows a higher affinity for the N-methyl-D-aspartate (NMDA) receptor than the r-enantiomer (18). Nie et al. randomly assigned 84 patients candidated of FB to propofol/remifentanil or propofol/esketamine for sedation and analgesia (14). Main indications included tuberculosis (33%), tumor inspection (26%) and pneumonia (25%). The combination of esketamine with propofol in FB yielded more stable intraoperative hemodynamics, lower dosage of propofol, lower transient hypoxia rate, fewer incidence of adverse events and greater bronchoscopists satisfaction. Recently, Ding reported a sample of 160 patients who underwent FB under general anesthesia who were randomly assigned to esketamine or fentanyl (15). The esketamine regimen yielded more stable hemodynamics, faster onset and recovery time of anesthesia, longer duration of analgesia, lower incidence of adverse reactions and improved early postoperative recovery quality. Apostolos et al. randomly assigned 50 patients scheduled for FB to a combination of midazolam-fentanyl vs. dexmedetomidine-ketamine in a prospective, single-blind, randomized controlled trial. They reported a good safety profile in patients subjected to FB and achieved more profound sedation and better bronchoscopist satisfaction without increasing the rate of adverse events with the administration of dexmedetomidine-ketamine (17).

Rigid bronchoscopic experiences with ketamine

For what regards RB in adult patients, there are very few reports about ketamine administration patients (summary available in Table 3). Almost all of them consist of case reports about patients with CAO where heterogeneous anesthetic combinations were applied (20-22). We found only a retrospective series of 52 patients that underwent a RB with Yag-laser treatment for benignant and malignant conditions. They were managed with TIVA based on ketamine or methohexitone infusion (19). Seventy-five RBs were carried out as some patient needed several procedures No death or major surgical complications occurred. Unfortunately it is not clear how many procedures were performed with the administration of ketamine or methohexitone. In this paper the oxygenation was carried out with venturi ventilation via the rigid bronchoscope equipment.

Type of ventilation

Several ventilation strategies are possible during RB to provide adequate oxygenation while maintaining appropriate sedation. (I) Apneic oxygenation, that consist of intermittent positive pressure ventilation via the rigid bronchoscope, requiring instrument removal from working port and oropharyngeal packing for complete sealing. (II) Spontaneous assisted ventilation (SAV) is a ventilation technique in which sedation levels are closely titrated during the procedure with short-acting drugs in order to maintain spontaneous breathing by the patient (23). In case of oxygen desaturation, supplemental oxygen is supplied through a side port of the rigid bronchoscope. (III) Controlled ventilation (closed system) where the rigid bronchoscope is used as an endotracheal tube to provide inhaled anesthetic under positive pressure ventilation. (IV) Jet ventilation, that is an high-pressure gas source applied with short bursts via a small-bore catheter. It could be manual or automated, depending on the respiratory rate target: the latter is also known as high-frequency jet ventilation (HFJV) (24).

Our methodology

The above mentioned literature evidence, in particular the ones about FB, reported interesting results about how ketamine usage positively affected safety, cardio-respiratory stability and compliance of patients. Some authors also focused on the operators’ satisfaction about the possibility to carry out the procedures without significant disturbance. Hence, we tried to merge these elements with a favourable experience at our institution with FB and EBUS-TBNA shifting all of them into the RB field. With the cooperation of our dedicated anesthesiologist team, we developed an anesthetic protocol for RB based on TIVA with ketamine addition (25). After preoxygenation for 5 minutes with 100% oxygen, TIVA was started with remifentanil target-controlled infusion (TCI) 0.5–3 ng/mL and ketamine (0.75–1 ng/kg). For the latter, an initial dosage of 50 mg was administered, followed by additional doses of ketamine (20 mg) and propofol (TCI 0.5–1.5 ng/mL) every 20–40 minutes until the end of the procedure. Our choice aimed to counteract the side effects of ketamine and midazolam (respiratory depression and hypotension for the later and respiratory stimulus and sympathomimetic effect for the former) and to lower the infusion rates of propofol and remifentanil, reducing their side effects. We firmly avoided NMBs in all cases. After intubation with the rigid bronchoscope, SAV was maintained throughout the procedure. We performed rigid bronchoscopic intervention in five patients: four of them were affected by lung cancer causing CAO due to intraluminal growth or extraluminal compression/infiltration; one patient suffered from postintubation tracheal stenosis. All the procedures were successful in restoring the airway patency and were uneventful. Our anesthetic protocol allowed us to comfortably manage the different performed procedures: 4 patients underwent stent placement (1 metal and 3 silicon) after rigid dilatation and argon plasma coagulation (APC); 1 patient did not need stenting because of significant airflow improvement after tumor debulking performed with APC. The patients were compliant and no general or drug-related side effects were reported. Vital signs were checked during and after surgery with SpO₂ maintaining almost always over 95%.

The operator point of view

RB for CAO is a very challenging procedure. Usually the patients who need RB have compromised respiratory function and suffer remarkably from breathlessness. Often, the patients have a poor long-term prognosis because of the underlying malignant disease. In addition, CAO may present in an acute and severe manner. All these items make a huge burden to cope with, both for the anesthesiologist and the interventional bronchoscopist. Therefore, it is of paramount importance to perform the RB in the most comfortable way. In this scenario, considering our institutional experience in FB and EBUS-TBNA for adult—both in scheduled and emergency or challenging setting (26)—and supported by the previous literary reports on ketamine administration, we designed our protocol management for RB. We noticed how ketamine usage yielded a very a remarkable comfort to the surgeon because of the patient’s deep stillness and compliance but also to the anesthesiologist because of the very infrequent desaturation occurrence and the haemodynamic stability achieved. Aware of the evidence lack in literature about ketamine administration for adult RB management, insight of our operators (surgeon and anesthesiologist) primarily lean on our multidisciplinary team meeting (27)—that is scheduled weekly for thoracic pathology discussion—and the deep and established experience with EBUS-TBNA and FB.

Conclusions

Reports about ketamine usage in adult RB are sporadic and no clear anesthesiologic approach is available. Ketamine addition on TIVA protocol seems to be safe and feasible for management of RB in adults. This drug regimen may be reliable in several possible interventions for malignant and benignant conditions. The comfort yield was remarkable both for the anesthesiologist and the surgeon. We suggest the planning of high quality and larger population studies to confirm if this protocol is eventually reliable for adult RB procedures.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1715/rc

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1715/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1715/coif). P.C. serves as an unpaid editorial board member of Journal of Thoracic Disease from November 2022 to January 2025. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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