Efficacy of gabapentin versus trospium chloride for prevention of catheter-related bladder discomfort inside the surgical intensive care unit: a prospective, randomised, controlled clinical study

Introduction

Patients with catheter-related bladder discomfort (CRBD) complain of symptoms almost identical to those of overactive bladder syndrome (OABS) such as; painful urinary irritation and burning in suprapubic and pelvic areas, frequency and/or urgency [1]. It can trigger serious behavioural reactions such as agitation, restlessness, delirium or even traumatic self removal of the catheter. Systemic responses such as hypertension and dysrhythmia can also occur with negative psychological impacts [2].

The main pathophysiology of CRBD and OABS is catheter-induced irritation of the bladder acetylcholine release, which stimulates urothelial M2 and M3 muscarinic receptors, leading to involuntary detrusor muscle contractions [3].

Antimuscarinic drugs including trospium chloride, darifenacin, solifenacin, tolterodine and oxybutynin are the first choice drugs for OABS, so they have been studied for the prevention of perioperative CRDB with variable degrees of success [4,5]. Trospium chloride drug is a non selective antimuscarinic agent that is effective in managing resistant cases of OABS [6]. Extended-release trospium chloride is also effective with the merit of a single daily dose [7].

Some antiepileptic drugs, such as pregabalin and gabapentin, have been also reported to be effective in managing resistant cases of OABS through the inhibition of up regulated bladder afferent C-fibres [8]. Therefore, both are used for prevention of CRDB, with subsidiary analgesic effect [9,10]. Additionally, other drugs are used in CRDB prevention such as ketamine, tramadol, paracetamol and dexmedetomidine [11,12,13,14]. We aimed to evaluate the efficacy of both gabapentin and trospium chloride in preventing CRBD during early postoperative period in patients who admitted to surgical intensive care unit (S-ICU) for postoperative care (POC) after undergoing elective spinal surgery (ESS) and requiring intraoperative catheterisation of the urinary bladder (COUB).

Materials and methods

Results

One hundred and thirty-one patients were assessed for eligibility, with an enrolment of 120 who completed the whole study (Figure 1).

Fig. 1.

There were no statistically significant differences regarding the patients' demographic data and clinical characteristics between group G, group T and group C (Table 1).

With respect to medical, surgical, and anaesthesia-related causes of postoperative S-ICU admission, there is no considerable difference between the three groups, with the medical causes being the main causes of POC in the S-ICU (Table 2). Additionally, there is no significant difference concerning the anatomical sites of spine surgeries, with the lumbar vertebral surgeries being the main sites in the three groups (Table 2).

Group C had a statistically significant higher incidence of CRBD (60%, 55%, 47.5%, 37.5%, and 25%) than group G (35%, 30%, 27.5%, 15%, and 10%) and group T (27.5%, 22.5%, 20%, 7.5%, and 5%) at 1, 2, 6, 12, and 24 hours after SDA, respectively (Table 3, Figure 2). Additionally, the severity of CRBD at 1, 2, 6, 12, and 24 hours after the SDA was higher in group C than in group G and group T; however, this difference was significant only in the first two hours (P= 0.001 and 0.001, respectively), (Figure 3 and 4). Severity was in-significantly lower in group T than in group G, with the occurrence of severe CRBD once in the first hour after SDA in group G (Table 3).

Fig. 2.

Fig. 3.

Fig. 4.

The visual analogue pain scale (VAS) was comparable amongst the three groups with an overall low median VAS. However, group G had statistically significantly lower VAS at 6 and 12 hours after SDA than group T and group C (P = 0.003 and 0.014, respectively), (Table 4 and Figure 5). Additionally, group G had significantly lower mean total fentanyl requirements in the initial 24 hours after SDA (850.07 ± 122.63 µg) than group T (1437.02 ± 103.67 µg) and group C (1425.58 ± 88.88 µg), (P < 0.001), (Table 4 and Figure 6). Finally, the side effects of the utilised drugs, including RSS, were minimal amongst the three groups without substantial difference, with an overall low mean RSS in groups G, T and C (2.38 ± 0.67, 2.23 ± 0.73, 2.08 ± 0.69, respectively), (Table 5).

Fig. 5.

Fig. 6.

Discussion

This single-centre, randomised, controlled trial illustrated that both the oral 400 mg gabapentin capsule and the slow-release trospium chloride 60 mg capsule administered postoperatively, after resumption of oral feeding, significantly reduced both the incidence and severity of CRBD in the early postoperative period (POP), amongst patients admitted to the S-ICU after undergoing ESS and who required COUB. Uniquely, gabapentin considerably reduced mean total fentanyl requirements.

Agreeing with our study results but with different intervention protocols, Agarwal et al. [17] also reported that the administration of 600 mg gabapentin orally one hour before induction of anaesthesia in patients who underwent percutaneous nephrolithotomy (PCNL), reduced the occurrence of postoperative CRBD (50%, 61%, 55%, and 37%) and its severity at 0, 1, 2 and 6 hours, respectively. It also significantly reduced the postoperative pain and the total fentanyl consumption.

In studies with similar methodology to Agarwal et al. [17] but in patients who underwent ESS, administration of oral 150 mg pregabalin [10] or 60 mg trospium chloride (ER) [18], markedly reduced the incidence of postoperative CRBD (36.6%, 36.6%, 30%, 16.6 % versus 22%, 28%, 22%, and 9%) and its severity at 0, 1, 2 and 6 hours, respectively. Pregabalin also led to a significant reduction in postoperative fentanyl consumption, but not trospium chloride.

Comparably, a study [16] reported that oral oxybutynin and tolterodine decreased the incidence of CRBD by 23–25 %, respectively. Also, Tauzin et al. [19] demonstrated a decrease in the incidence of CRBD by 48% after radical prostatectomy using oxybutynin sublingually. However, a mixed drug effect was obtained, as 600 mg oral gabapentin was used as a premedication and 100 mg IV tramadol was used during wound closure. Both of these drugs also lower the occurrence of CRBD.

We selected spinal surgery for our study to avoid the confusion in differentiating the CRBD from pain or spasm associated with genitourinary surgery.

Moreover, we administered the study drugs to patients orally after their full anaesthesia recovery, transfer and admission to the S-ICU. This isolates the effect of drugs used in general anaesthesia which may influence the incidence of CRBD. Two studies [20,21] revealed that the use of IV glycopyrrolate just as a premedication or as a part of a reversal drug to antagonise neuro-muscular blockade decreased the incidence of CRBD. Additionally, another two studies [22,23] reported that inhalational sevoflurane decreased the incidence of immediate postoperative CRBD (up to 1 hour) compared with desflurane and propofol.

Furthermore, we administered slow release (SR) 60 mg trospium chloride, first for its long action and second because 60 mg is the most efficient once-daily dose for management of OABS [24]. Also, we administered 400 mg gabapentin, first for its long action and second because its initial doses range from 100 to 300 mg for most painful syndromes, such as post-herpetic neuralgia, neuropathic pain, fibromyalgia, and restless leg syndrome.

Conversely, Agrawal et al. [17] administered 600 mg gabapentin to patients who underwent elective PCNL, whereas Bala et al. [9] administered either 600 mg or 1200 mg gabapentin capsules to patients who underwent transurethral resection of bladder tumours. These larger doses may be needed because of the associated visceral pain and spasm with urological surgeries, which mimic CRBD.

In our study, both drugs were safe with minimal side effects and without significant differences between them. Dry mouth occurred in two patients (5%) in group G, four patients (10%) in group T and one patient (2.5%) in group C. Additionally, there was no excessive sedation, as a RSS of 2 may be advantageous rather than a side effect, as the patient is awake, oriented, cooperative, and tranquil and does not interfere with the CRBD assessment.

Previous study [16] revealed a greater incidence of dry mouth peaking at one hour postoperatively in the oxybutynin arm (58.9%) and in the tolterodine arm (55.1%). Srivastava et al. [10] also reported sedation by utilising oral pregabalin with a mean RSS of 2.63 ± 0.67.

This study has limitations. First, gabapentin was approved by the Food and Drug Administration (FDA) to manage certain forms of neuropathic pain, post-herpetic neuralgia, fibromyalgia, and partial seizures but not for treating urologic dysfunction compared to trospium chloride, which is used for management of OABS. However, gabapentin is utilised off-label for management of neurogenic detrusor overactivity [25] and refractory genitourinary tract pain [26]. Second, we used oral drugs that cannot be taken by patients with prolonged NPO (nil per os) status. Third, we used fixed doses for both drugs, so further studies with multiple lower doses are needed to evaluate the dose response titration and the minimal effective doses for preventing CRBD with the least side effects. Finally, this was a single-centre study of patients admitted to S-ICU. Further multicenter studies on more patients and on patients in different ICUs (e.g. medical, cardiac, or neurological ICUs) are needed for the generalisation of the results.

Conclusion

Both oral gabapentin 400 mg capsule and slow release trospium chloride 60 mg capsule administered postoperatively markedly decreased the incidence of CRBD and its severity in the early postoperative period amongst patients admitted to the S-ICU for POC after undergoing ESS and requiring COUB, compared to non-pharmacological standard of care after COUB, without a significant difference between the two drugs, and with minimal side effects. Uniquely, gabapentin significantly reduced the total fentanyl consumption compared to trospium and non-pharmacological standards of care after COUB.