Use of esketamine for tracheoscopic drug injection: a clinical study

doi:10.21203/rs.3.rs-3998990/v1

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Use of esketamine for tracheoscopic drug injection: a clinical study

https://doi.org/10.21203/rs.3.rs-3998990/v1

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Background

To assess the feasibility and safety of ketamine for tracheoscopic drug injection and identify an effective and safe anesthetic method.

Methods

This study included 100 patients who required painless bronchoscopy and endoscopic drug injection at our hospital from January 2020 to March 2021. Patients were randomly divided into two groups (n = 50 each): Group A received esketamine and Group B received sufentanil. During anesthesia induction, propofol and atracurium at mg/kg and 0.4 mg/kg doses were intravenously administered. Groups A and B received intravenous esketamine and sufentanil at mg/kg and 0.2 µg/kg doses, respectively. A laryngeal mask was inserted and connected to the anesthesia machine for mechanical ventilation. Anesthesia was maintained by continuous intravenous infusion of propofol at 3 mg/kg. Changes in oxygen saturation, blood pressure, surgical duration, and awake time were assessed and recorded in all patients before and after anesthesia induction.

Results

The anesthetic effect in Group A was significantly better than that in Group B (P < 0.05). There was no significant difference concerning respiration inhibition between Groups A and B (P > 0.05). The awake time of Group A was significantly earlier than that of Group B (P < 0.05). The effect of anesthesia on blood pressure and heart rate in Group A was lesser than that in Group B (P < 0.05).

Conclusion

The anesthetic effect of ketamine combined with propofol in painless bronchoscopy injection for diagnosis and treatment is good. In clinical practice, the appropriate compatible drug can be selected based on the patient’s vital signs. Hence, the patients can undergo a smooth and comfortable surgery.

Trial registration

Chinese Clinical Trial Registry

Name of Registration: Chinese Clinical Trial Registry

The registration number is：ChiCTR2000039902

Date of Registration: 22/12/2020

Esketamine

Sufentanil

Tracheoscopy

Curative effect

Security

Malignant tumor cells invade the trachea, leading to malignant tracheal stenosis, which can cause dyspnea and is considered a severe respiratory disease. Therefore, the treatment primarily aims to immediately eliminate airway obstruction. Previous studies have shown that the intratumoral injection of cisplatin and Endostar, especially when combined with cryotherapy and hyperthermia, under a bronchoscope can eliminate tumors, control tumor growth, maintain a smooth trachea and bronchial lumen in a timely manner, and prolong the time of tracheal restenosis [1–2]. However, it can also lead to several issues. Patients can feel uncomfortable during the treatment, particularly in the long-term treatment process, and cannot be treated or treatment fails due to lack of cooperation. To improve the comfort and efficacy of examination and treatment, general anesthesia is preferred. In this anesthetic method, sufentanil is commonly used in the induction stage. However, the use of sufentanil in elderly patients can often cause adverse events such as cough, chest wall stiffness, hypotension, and bradycardia [3], which can affect surgeries using a tracheoscope. Esketamine is the dextral structure of ketamine, which has effects including sedation, analgesia, and loss of consciousness. However, it has a minimal effect on respiration and circulation [4]. Therefore, this study evaluated the efficacy and safety of ketamine combined with propofol for painless tracheoscopy in patients with tumors to provide a reference for clinical medication.

Clinical data: We collected the data of 100 patients who underwent painless bronchoscopy and received injection therapy from March 2020 to July 2021 at the Department of Respiratory and Critical Care Medicine, Qingdao Haici Hospital Affiliated to Qingdao University. The trial was registered with the Chinese Clinical Trial Registry under the name "Chinese Clinical Trial Registry" with registration number ChiCTR2000039902 on 22/12/2020. All patients presented with The American Society of Anesthesiologists (ASA) classification I–II disease. However, none of the patients were at high risk for anesthesia. Inclusion criteria: The inclusion criteria were as follows: patients with lung cancer, lung metastases, and tracheal tumors confirmed on pathology and/or cytology who had central airway lesions that were intratracheal + wall or wall type, those who required painless bronchoscopy and injection therapy under a bronchoscope, and those aged over 60 years. Exclusion criteria: The exclusion criteria were as follows: patients allergic to narcotic drugs; those who refused to undergo tracheoscopy; those with uncontrolled hypertension, cerebral infarction within the last 3 months, oral anticoagulants, new cardiovascular events, and oral antiplatelet drugs that cannot be discontinued; those with severe respiratory insufficiency or cardiac insufficiency who could not tolerate tracheoscopy and treatment; and those with vital signs that changed due to excessive bleeding during surgery. The participants were randomly divided into group A who included patients receiving esketamine (n = 50) and group B who comprised patients receiving sufentanil (n = 50).

Anesthetic methods: During anesthesia induction, propofol at a dose of mg/kg and atracurium at a dose of 0.4 mg/kg were intravenously administered. Group A received esketamine at a dose of mg/kg intravenously. Group B received sufentanil at a dose of 0.2 µg/kg intravenously. A laryngeal mask was inserted and connected to the anesthesia machine for mechanical ventilation. Anesthesia was maintained via continuous intravenous infusion with propofol at a dose of 3 mg/kg.

Surgical method using the tracheoscope: The patients were treated with a bronchoscope injection needle (Shanghai Elton Model: af-d1810pn). Routine bronchoscopy was performed. After cutting the tumor under a bronchoscope, the needle was inserted into the residual tumor under direct visualization. Injection was performed at 4–6 points at the center and periphery of the tumor. The penetration depth was 3–4 mm. Endostar (15 mg) and cisplatin (20 mg) were diluted to 4 mL. Four to six parts of the tumor were injected alternately with 0.5 mL of drugs each time, twice a week for two consecutive weeks.

Observation index: The systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), oxygen saturation, and recovery time of the patients were recorded before anesthetic injection (T0), after laryngeal mask insertion (T1), at 5 min after surgery (T2), at 15 min after surgery (T3), and before the end of surgery (T4). The adverse reactions of the patients after drug injection were recorded.

Quality control plan: All examinations were performed by the same physician and assistant and by the same anesthesiologist. The adverse reactions were recorded by the anesthesia assistant who was not knowledgeable about the patient grouping.

Statistical processing: The Statistical Package for the Social Sciences software version 23.0 was used for statistical analysis. The t-test was used to compare the two groups. The comparison between the two groups was performed using χ2. A P value of < 0.05 was considered significant.

There were no significant differences in terms of age, sex, body mass index, and ASA classification (I/II) between the two groups (P > 0.05), as shown in Table 1.

Table 1

Comparison of baseline data between groups A and B
Baseline indicators	Group A	Group B	P value
Sex (M/F 例)	32/18	29/21	0.681
Age (years)	60–79	60–81	0.796
BMI (x ± s), kg/m²	23.2 ± 2.3	23.6 ± 2.7	0.427
ASA classification I/II	19/31	22/28	0.068

The recovery time from anesthesia in group A was lower than that in group B (P < 0.05). There was no significant difference in terms of surgical duration between the two groups (P > 0.05), as shown in Table 2.

Table 2

Comparison of surgical duration and anesthesia recovery time between groups A and B
Group	Number of cases	Surgical duration (x ± s), min	Anesthesia recovery time (x ± s), min
Group A	50	23.74 ± 5.7	3.6 ± 1.3
Group B	50	22.56 ± 6.3	4.1 ± 1.1
P		0.329	0.04

The SBP, DBP, and HR of group A were significantly higher at T1, T2, T3, and T4 than at T0 (P < 0.05). The SBP, DBP, and HR of group B were significantly lower at T1, T2, T3, and T4 than at T0 (P < 0.05). There was no significant difference in terms of oxygen saturation at each time point during the surgery between the two groups, as shown in Table 3.

Table 3

Vital signs recorded at different time points
Vital signs	Group	Number of cases	T0	T1	T2	T3	T4
SBP (mmHg)	A	50	132.52 ± 8.22	136.41 ± 7.33	140.55 ± 9.65	141.66 ± 7.60	142.27 ± 7.49
SBP (mmHg)	B	50	129.63 ± 5.63	126.62 ± 8.53	120.32 ± 8.63	115.38 ± 8.92	115.12 ± 8.52
DBP (mmHg)	A	50	86.75 ± 6.32	90.55 ± 4.11	94.13 ± 7.35	95.66 ± 4.97	96.71 ± 4.33
DBP (mmHg)	B	50	88.65 ± 7.69	83.12 ± 8.96	80.31 ± 5.67	80.22 ± 5.33	79.92 ± 8.44
HR (bpm)	A	50	90.42 ± 5.98	92.56 ± 9.66	96.22 ± 4.55	97.26 ± 8.52	97.11 ± 4.38
HR (bpm)	B	50	92.21 ± 6.22	90.16 ± 7.44	85.31 ± 8.66	82.11 ± 6.99	81.49 ± 5.39
SpO₂ (%)	A	50	96.63 ± 0.65	95.56 ± 0.73	96.77 ± 0.52	97.88 ± 0.71	97.72 ± 0.45
SpO₂ (%)	B	50	97.25 ± 0.56	96.87 ± 0.46	96.82 ± 0.28	97.12 ± 0.21	96.98 ± 0.33

Endotracheal interventional therapy under a bronchoscope is safe, effective, and minimally invasive. It has increasingly prominent advantages for treating airway tumors. For patients with definite malignant intratracheal tumors, intratumoral injection of chemotherapy drugs combined with cryotherapy and hyperthermia can play a synergistic role. In previous studies, our team confirmed that drug injection under a bronchoscope can immediately and effectively remove the airway tumor and prolong the time of airway restenosis. However, because bronchoscopy should go deep into the human body, it is an invasive examination that can cause significant discomfort, not only cough but also dyspnea and other serious complications [5]. It also leads to operational difficulties and risks to the medical staff [6].

Laryngeal mask airway anesthesia can ensure the airway patency of patients. Hence, they can complete the surgery comfortably. The anesthesia operation stimulation is minimal [7], particularly after applying lidocaine cream. Moreover, the insertion and removal of a laryngeal mask has minimal effects on circulation. General anesthesia can relax the pharyngeal muscles and shorten the surgical duration. At present, opioids are commonly used. However, in the process of anesthesia induction, the blood pressure of patients with hypotension and low HR decreases significantly. Further, vasoactive drugs are required to maintain blood pressure within the normal range.

Esketamine is the dextral structure of ketamine and is more effective. It has three functions: sedation, analgesia, and forgetting. Moreover, it can be used as a sedative for anesthesia induction and general anesthesia [8]. Simultaneously, anesthesia can relax the bronchial smooth muscle. Clinically, it works via intravenous injection for 30 s and can last for approximately 30–45 min. This clinical controlled study found that ketamine has the following advantages: First, it has an accurate anesthetic effect, and a single injection can meet the surgical requirements. Second, it did not affect the recovery of spontaneous breathing and almost did not delay the recovery. However, it may lead to increased blood pressure and HR [9]. However, it also has disadvantages. For example, the blood pressure and HR of the patients increased significantly at the start of surgery.

Sufentanil, an opioid, takes effect 1.5 min after one injection and lasts approximately 40 min. If the dose exceeds the recommended dose, transient respiratory depression may occur. Combined with propofol, it can increase respiratory and circulatory depression, thereby indicating dose-dependent tolerance [10]. The advantages of this controlled trial are as follows: First, the analgesic effect is accurate, and a single injection can meet the operation requirements. Second, the recovery of spontaneous respiration was almost unaffected, and recovery was not delayed. However, the main adverse reactions of sufentanil are hypotension and bradycardia [11]. In this study, several disadvantages were observed. That is, the blood pressure of patients had a downward trend from anesthesia induction to the end of the surgery.

In this clinical study, the time from anesthesia induction to laryngeal mask insertion to the beginning of surgery was extremely short. Therefore, there was no observation time point between anesthesia induction and the start of interventional surgery.

Both ketamine and sufentanil can be used as anesthesia for injection therapy under an electronic bronchoscope. However, the effects of these two drugs on blood pressure and HR differ. In clinical practice, the appropriate compatible drug can be selected based on the patient’s vital signs. Therefore, patients can undergo a smoother and more comfortable surgery.

ASA, American Society of Anesthesiologists

SBP, systolic blood pressure

DBP, diastolic blood pressure

HR, heart rate

Ethics approval and consent to participate: The study was approved and approved by the Ethics Committee of Qingdao Haizi Hospital affiliated to Qingdao University (2020HC12LS011) on 22/12/2020. Written informed consent was obtained from the patient or parent/guardian/relative of the patient for the participation in the study

Consent for publication: Written informed consent was obtained from the patient/parent/guardian/relative of the patient for the publication of clinical details and/or images.

Availability of data and materials: The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Competing interests: The authors declare that they have no competing interests.

Funding: Not applicable

Authors’ contributions: XmZ (the first author): major contributor in writing the manuscript, contributed data; Zd Z (the second author): contributed data, data collection; ZhL (the third author): data collection, performed the analysis; YyY (the fourth and the corresponding author): conceived and designed the analysis. All authors have read and approved the final manuscript.

Acknowledgements: The authors thank Hu Zhaolan, post-doc, Central South University Xiang YA II hospital, Department of Anesthesia；Deputy Director of anesthesiology, Qingdao Haizi Hospital affiliated to Qingdao University.ORCID:0000-0003-1137-0579.

Huret B, Perez T, Dhalluin X, Dewavrin F, Ramon PP, Fournier C. Treatment of malignant central airways obstruction by rigid bronchoscopy. Rev Mal Respir. 2015;32:477-84. doi:10.1016/j.rmr.2013.09.018.
Jiang W, Yang X, Wang X, Li Y , Yang X, Wang N, et al. Bronchoscopic intratumoral injections of cisplatin and endostar as concomitants of standard chemotherapy to treat malignant central airway obstruction. Postgrad Med J. 2020;98:104-12.doi: 10.1136/postgradmedj-2020-138823
Agarwal A, Gautam S, Nath SS, Gupta D, Singh U. Comparison of the incidence and severity of cough induced by sufentanil and fentanyl: a prospective, randomised, double-blind study. Anaesthesia. 2007;62:1230-2. doi:10.1111/j.1365-2044.2007.05249.x.
Pfenninger EG, Durieux ME, Himmelseher S. Cognitive impairment after small-dose ketamine isomers in comparison to equianalgesic racemic ketamine in human volunteers. Anesthesiology. 2002;96:357-66. doi:10.1097/00000542-200202000-00022.
Leiten EO, Martinsen EM, Bakke PS, Eagan TM, Grønseth R. Complications and discomfort of bronchoscopy: a systematic review. Eur Clin Respir J. 2016;3:33324. doi:10.3402/ecrj.v3.33324.
Ballantyne B. Medical management of the traumatic consequences of civil unrest incidents: causation, clinical approaches, needs and advanced planning criteria. Toxicol Rev. 2006;25:155-97. doi:10.2165/00139709-200625030-00003.
Kotsovolis G, Pliakos I, Panidis S, Gkinas D, Papavramidis T. Comparison between the Protector™ laryngeal mask airway and the endotracheal tube for minimally invasive thyroid and parathyroid surgery. World J Surg. 2019:2822-8. doi:10.1007/s00268-019-05122-8.
van de Bunt JA, Veldhoen ES, Nievelstein RAJ, Hulsker CCC, Schouten ANJ, van Herwaarden MYA. Effects of esketamine sedation compared to morphine analgesia on hydrostatic reduction of intussusception: a case-cohort comparison study. Paediatr Anaesth. 2017;27:1091-7. doi:10.1111/pan.13226.
Eberl S, Koers L, van Hooft JE, de Jong E, Schneider T, Hollmann MW, et al. Sedation with propofol during ERCP: is the combination with esketamine more effective and safer than with alfentanil? Study protocol for a randomized controlled trial. Trials. 2017;18:472. doi:10.1186/s13063-017-2197-8.
Yu Y, Qi SL, Zhang Y. Role of combined propofol and sufentanil anesthesia in endoscopic injection sclerotherapy for esophageal varices. World J Gastroenterol. 2017;23:7875-80. doi:10.3748/wjg.v23.i44.7875.
Gao J, Wei L, Xu G, Ren C, Zhang Z, Liu Y. Effects of dexmedetomidine vs sufentanil during percutaneous tracheostomy for traumatic brain injury patients: a prospective randomized controlled trial. Med (Baltim). 2019;98:e17012. doi:10.1097/MD.0000000000017012.

No competing interests reported.

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Use of esketamine for tracheoscopic drug injection: a clinical study

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Abstract

Background

Methods

Results

Discussion

Conclusions

Abbreviations

Declarations

References

Additional Declarations

Status:

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