In the present study, we observed that 0.5 μg/kg dexmedetomidine intravesical instillation can significantly reduce the symptoms of postoperative catheter-related bladder discomfort and the urethral pain caused by catheter in male patients who received general anesthesia, and consequently, their satisfaction was improved. The improvement of these symptoms can sustain from 0.5-24 h after intravesical dexmedetomidine instillation.
CRBD is common in PACU, especially male patients[26]. Therefore, in this study, we included male patients as the study subject, and the incidence of CRBD was 65.2%, which was consistent with that reported previously[1, 2, 26]. The high incidence of CRBD in male patients might be related to the anatomical characteristics, such as the long urethra and large catheter[26]. Because several urological operations need to operate on the urethra, which markedly impacts this study, and the degree of impact is different, so this study was not included in the urological patients. In the clinical practice, to deal with bladder catheter pain, we often scribble lidocaine cream at the urethral orifice, meanwhile intravenous analgesic drugs, such as fentanyl, flurbiprofen axetil could also be used, but the effect is not ideal.
In this study, we observed that intravesical dexmedetomidine instillation can significantly reduce the symptoms of postoperative CRBD according to the following underlying mechanism. Alpha 2-adrenoceptor, i.e., the α2A-subtype, is expressed in the bladder, urethra, and prostate. The intra-arterial administration of an α-2 agonist reduced the micturition pressure, bladder capacity, and micturition volume[27, 28]. dexmedetomidine is a high selective adrenergic α-2 receptor agonist which may reduce the micturition pressure, bladder capacity, and micturition volume. There are several muscarinic receptors in bladder epithelium and efferent nerves, including M2 and M3. The M3 receptor is mainly responsible for bladder contraction[29]. The catheter can stimulate the afferent nerves of the bladder to release acetylcholine, which leads to the contraction of detrusor mediated by muscarinic receptors. Therefore, muscarinic antagonists alleviate CRBD in different degrees[1]. Some studies showed that dexmedetomidine might reduce bladder contractility via α-2 receptor and M3 muscarinic receptor antagonism[16, 17]. On the other hand, catheter stimulation can cause inflammation and increase prostaglandin secretion, which is one of the plausible reasons for CRBD[30]. Therefore, some anti-inflammatory drugs can also alleviate CRBD. Another study showed that dexmedetomidine reduces the release of prostaglandins of inflammation, and hence, relieves CRBD[31]. In addition, dexmedetomidine exerts a sedative effect and relieves CRBD[10]. Another underlying mechanism is that after intravesical instillation, dexmedetomidine can be absorbed from bladder and play a systemically role of sedation, analgesia and anti-inflammatory, which need to be further verified.
In the current study, dexmedetomidine plays a role in intravesical instillation. The off-label method of dexmedetomidine is often used in clinical research, which has proved to be safe and effective. For example, dexmedetomidine is safely used in subarachnoid and epidural[32], neuraxial[33] and for children intranasal[34]. As a safe and widely used drug, intravesical dexmedetomidine instillation method has been approved by the Institutional Review Board and Hospital Research Ethics Committee. Several studies[23-25] showed that intravesical instillation is an effective way of administration of drugs, which had an obvious effect on the treatment of bladder-related diseases and reduce the systemic response. For instance, invasive immunotherapy, chemotherapy and chemohyperthermia for bladder cancer[35, 36], intragastric thermal gelatin matrix implantation for intractable hematuria[37], intragastric gentamicin for recurrent urinary tract infections treatment[38]. Dexmedetomidine is well absorbed through the mucous membrane. Iirola et al.[39] reported that peak plasma concentrations of dexmedetomidine were 38 min after intranasal administration, and the pharmacological effects were similar to the intravenous administration but with a later onset time. In the current study, dexmedetomidine was able to work through the bladder mucosa, with a significant effect at half an hour after administration. Even so, intravesical dexmedetomidine instillation has potential risk of bladder dysfunction such as urinary retention through a local α2-stimulating effect, which should be closely pay attention in clinical practice.
In this study, intravesical dexmedetomidine instillation alleviates the pain caused by catheter while in situ and on removal. The main causes of the pain during catheter in situ were as follows: the material and size of the catheter, the traction of the catheter drainage bag, the urethral discomfort, the stimulation of the bladder wall by the catheter, the obstruction of the catheter, catheter blockage, the hemorrhagic pseudopolyps, the fear of the catheter, and the psychological rejection[40]. In the present study, all patients were observed and nursed closely, and the material and size of the catheter were identical, and no catheter drainage bag traction, catheter obstruction, hemorrhagic pseudopolyps were observed. Therefore, we speculated that the main reason for the difference in the urethral pain between the two groups was the tolerance of catheter stimulation of the bladder wall and the difference in the fear and psychological rejection of the catheter. Dexmedetomidine is a solution to bladder irritation and psychological maladjustment of patients, thereby reducing the catheter-induced urethral pain. Systematic pain NRS score decreased at T4, and there was no significant change at other time points. The possible reason is that dextromethorphan was absorbed by bladder and played a systemic role, which need further study.
Patients’ satisfaction at the time point out of PACU and 24 h after the operation was significantly improved after intravesical dexmedetomidine instillation because there were reductions in CRBD and catheter-induced urethral pain and patient satisfaction is closely related to the postoperative outcomes[41]. The improvement in the patients’ satisfaction might reduce their CRBD and urethral pain.
No complications were detected in the control and experimental groups. Since the sample size of this study is small, and the patients selected are ASA I-II, their basic conditions are well. Clinically, we will encounter CRBD to aggravate the condition of patients with coronary heart disease, and dexmedetomidine might also lead to arrhythmia and other risks. What is more, intravesical dexmedetomidine instillation perhaps could prolong bladder dysfunction through a local α2-stimulating effect and dexmedetomidine still reduces CRBD after 24 hours. There was no urinary retention or re-catheterisation complication in dexmedetomidine group. However, only 9 ureteral catheters were removed at 6 to 12 hours after operation, and 38 catheters were removed at 12 to 24 hours in this study. The safety of the intravesical dexmedetomidine instillation need further clinical validation.
Nevertheless, the present study has some limitations. The number of cases is small as only 167 patients were included in this single-center study. In the future, large sample and multi-center clinical verification is essential. The patients included in this study were male patients with catheter placement under general anesthesia. The type of operation is not uniform, and the duration of operation is varied. This study did not limit the factors such as midazolam and operation time, and did not make further subgroup analysis. Further subgroup study can be carried out after expanding the sample size in the future. Prolonged follow-up for bladder dysfunction was not implemented. The safety of intravesical dexmedetomidine instillation should be further studied. It is not sure if systemic dexmedetomidine has the same effect for CRBD, further research should include an arm with intravenous dose of dexmedetomidine. All the patients included in this study were ASA I-II patients with elective surgery, and the basic condition of the patients was good. Also, critical patients have not been analyzed previously. Moreover, the effect of different doses of dexmedetomidine on CRBD was not assessed in this study. Ten milliliter normal saline was injected into the cuff balloon of catheter for all paitents to prevent slippage in our research. This may also be a potential cause of bladder wall irritation. It is regretful that we did not follow up with further research on the effect of reducing the balloon volume for reducing CRBD.