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Table of Contents  
ORIGINAL ARTICLE
Year : 2016  |  Volume : 10  |  Issue : 3  |  Page : 613-617  

Evaluation of efficacy of amikacin for attenuation of catheter-related bladder discomfort in patients undergoing percutaneous nephrolithotomy: A prospective, randomized, placebo-controlled, double-blind study


1 Department of Anesthesiology, T S Mishra Medical College and Hospital, Amausi, Lucknow, Uttar Pradesh, India
2 Department of Anesthesiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India

Date of Web Publication27-Sep-2016

Correspondence Address:
Ruchi Verma
C2/402, Akash Enclave, Sector 6A, Vrindavan Yojna, Lucknow, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0259-1162.191116

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   Abstract 


Context: Catheter-related bladder discomfort (CRBD) is the most distressing symptom in patients due to intraoperative urinary catheterization. Amikacin significantly inhibits detrusor contraction evoked by prejunctional stimulation.
Aims: The aim of this study is to evaluate the efficacy of amikacin in prevention of CRBD in patients undergoing percutaneous nephrolithotomy.
Settings and Design: Study areas were operation theater and postanesthesia care unit of the Department of Anesthesiology, SGPGIMS, Lucknow.
Subjects and Methods: One hundred adult patients of either sex were randomly assigned into two groups of fifty each. Patients in control group received normal saline whereas patients in amikacin group received amikacin 10 mg/kg just before induction. Grading of CRBD was done as none, mild, moderate, and severe by a blinded observer at 0, 1, 6, 12, and 24 h after surgery.
Statistical Analysis Used: Data were analyzed using Student's t-test and Chi-square test among groups. Incidence of CRBD was compared with Chi-square test whereas severity was analyzed by the test of proportions (Z-test). Visual analog score was compared using Mann–Whitney U-test for surgical site pain.
Results: Incidence of CRBD in control group was 66% as compared to 44% observed in amikacin group (P < 0.05). During intergroup comparison at different time points, incidence of CRBD was reduced at 1 and 6 h in the amikacin group (P < 0.05). Significant reduction in the severity of CRBD (moderate) was also observed at 1 h in the amikacin group (P < 0.05). At rest of the time points, there was no significant difference.
Conclusions: Amikacin can significantly reduce the incidence and severity of CRBD in the first few hours after surgery.

Keywords: Amikacin, catheter-related bladder discomfort, percutaneous nephrolithotomy


How to cite this article:
Verma R, Agarwal A, Singh PK, Gupta D, Shamim R. Evaluation of efficacy of amikacin for attenuation of catheter-related bladder discomfort in patients undergoing percutaneous nephrolithotomy: A prospective, randomized, placebo-controlled, double-blind study. Anesth Essays Res 2016;10:613-7

How to cite this URL:
Verma R, Agarwal A, Singh PK, Gupta D, Shamim R. Evaluation of efficacy of amikacin for attenuation of catheter-related bladder discomfort in patients undergoing percutaneous nephrolithotomy: A prospective, randomized, placebo-controlled, double-blind study. Anesth Essays Res [serial online] 2016 [cited 2020 Aug 14];10:613-7. Available from: http://www.aeronline.org/text.asp?2016/10/3/613/191116




   Introduction Top


Catheter-related bladder discomfort (CRBD) is defined as an urge to void or discomfort in the suprapubic region, observed after operation in patients who awaken from anesthesia and have had urinary catheterization during operation.[1] This symptom complex is extremely distressing to a patient in the postoperative setting and may lead to exacerbated postoperative pain and reduced quality of life.[2] Symptoms of CRBD secondary to an indwelling urinary catheter mimic those of an overactive bladder (OAB), i.e., urinary frequency, urgency, with or without urge incontinence which are caused by involuntary contractions of the bladder mediated by muscarinic receptors.[3],[4]

A number of studies done using different drugs such as tolterodine, oxybutynin, gabapentin, ketamine, tramadol, butorphanol, resiniferatoxin, paracetamol, butylscopolamine, pregabalin, and dexmedetomidine have been reported to be effective in preventing CRBD in patients undergoing urologic surgeries.[5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15]

Amikacin was shown to have blocking actions on both autonomic and neuromuscular transmissions. The autonomic effects were caused mainly by ganglion blockade and were reversed by calcium. Aminoglycosides may inhibit not only prejunctional release of acetylcholine but also reduce postsynaptic sensitivity to the transmitter.[16]

It has been observed in an animal study that amikacin significantly inhibits detrusor contraction evoked by prejunctional stimulation in vitro, suggesting a depressant effect on autonomic neurotransmission in the urinary bladder.[17] The efficacy of amikacin in the prevention of CRBD in human individuals has never been studied. We therefore planned this study to evaluate the efficacy of amikacin in prevention of CRBD in patients undergoing percutaneous nephrolithotomy (PCNL) requiring intraoperative catheterization of the urinary bladder.


   Subjects and Methods Top


After approval from the Institute's Ethics Committee and patient's written informed consent, this prospective, randomized, placebo-controlled, double-blind study was conducted. Assuming that amikacin would reduce the incidence of CRBD by 30%, power analysis with α = 0.05, β = 0.19, we would need to study 43 patients in each group. To make provision for dropouts if any, we enrolled fifty patients in each group. The study therefore consisted of 100 consecutive adults (18–60 years) of American Society of Anesthesiologists Physical Status I and II patients of either sex, undergoing elective PCNL for renal and upper ureteric stone. Patients with history of outflow obstruction, transurethral resection of prostate for benign prostatic hyperplasia, history of bladder catheterization within the last 6 months, relook PCNL, preexisting percutaneous nephrostomy, deranged renal function, unsterile urine on culture, elderly patients (age >60 years), overactive bladder (frequency >3 times in the night or >8 times in 24 h), end-stage renal disease (urine output <500 ml per 24 h), morbid obesity, disturbance of the central nervous system, chemical substance abuse, chronic pain, and cardiovascular, hepatic, or any psychiatric disease were excluded from the study. Patients who could not be extubated at the end of the surgery or who were reexplored within the study period were considered as dropouts.

Patients meeting the inclusion criteria during the preanesthetic checkup were randomly assigned into two groups of fifty each with the help of computer-generated table of random numbers. Depending on the results of randomization, patients received medications just before induction. Patients in Group 1 (control) received Augmentin ® (amoxicillin/clavulanate potassium) 1.2 g and normal saline, whereas patients in Group 2 (amikacin) received Augmentin ® 1.2 g and amikacin 10 mg/kg. These medications were administered by a blinded anesthesia registrar who was not involved in the study.

All patients were premedicated with oral lorazepam 0.04 mg/kg and ranitidine 150 mg the night before and 2 h before surgery with sips of water. On arrival to operation room, intravenous (IV) assess was achieved with 18-gauge venous cannula under local anesthesia. Monitoring consisted of 5-lead electrocardiography, pulse oximeter, noninvasive blood pressure, temperature, and end-tidal CO2. Following preoxygenation with 100% oxygen, patients were induced with fentanyl 2–3 µg/kg and propofol 2–3 mg/kg. Tracheal intubation was facilitated by vecuronium bromide 0.1 mg/kg. Urinary catheterization was done with a 16 Fr Foley's catheter, and its balloon was inflated with 10 ml distilled water after induction of anesthesia. K-Y jelly (a water-based lubricating gel) was used to lubricate the catheter which was later fixed in the suprapubic area with an adhesive tape without any traction and will always be left to free drainage. Anesthesia was maintained using 70% nitrous oxide in oxygen and propofol infusion at 50–150 µg/kg/min and intermittent boluses of fentanyl and vecuronium as and when required. At the end of the surgery, the neuromuscular blocking agent was antagonized with a combination of neostigmine 0.05 mg/kg and glycopyrrolate 0.01 mg/kg and the patients were transferred to the postanesthesia care unit (PACU). In PACU, all the patients received fentanyl IV for their postoperative pain management using patient-controlled analgesia.

Assessment was done in terms of incidence and severity of CRBD. Severity of CRBD was recorded as:

  • None - when patient did not complain of any CRBD even on asking
  • Mild - when CRBD is reported by the patients only on questioning
  • Moderate - when it is reported by the patients on their own (without questioning and not accompanied by any behavioral response)
  • Severe - when it is reported by patients on their own along with behavioral responses (flailing limb, vocal response, and attempt to pull out catheter).[9]


Incidence and severity of CRBD were assessed at 0, 1, 6, 12, and 24 h after completion of the surgery.

The method of statistical analysis was decided prospectively and incorporated into the intention-to-treat principle. Patient characteristic data were analyzed with Student's t-test for continuous variables and Chi-square test for categorical variables. Data regarding incidence of CRBD were compared with Chi-square test, whereas severity of CRBD was analyzed by test of proportions (Z-test). Visual analog score (VAS) was compared using Mann–Whitney U-test for surgical site pain. SPSS 15.0 (SPSS Inc., Chicago, IL, USA) was used for statistical analysis. P < 0.05 was considered statistically significant.


   Results Top


A total of 100 patients were evaluated and received medication after randomization. There were no dropout cases. There was no substantial difference among the groups in regard to age, weight, height, duration of surgery, and intraoperative and postoperative fentanyl requirement (P > 0.05) [Table 1].
Table 1: Patient details, intra.operative and post.operative fentanyl consumption. Data are numbers or mean. (SD)

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Incidence of CRBD in control group was 66% as compared to 44% observed in amikacin group (P < 0.05). During intergroup comparison at different time points, incidence of CRBD was reduced at 1 and 6 h in the amikacin group (P < 0.05). Significant reduction in the severity of CRBD (moderate) was observed at 1 h in the amikacin group (P < 0.05). At rest of the time points, there was no significant difference in the severity of CRBD between the two groups (P > 0.05) [Table 2].
Table 2: Incidence and severity of CRBD presented as numbers and postoperative pain (VAS) presented as median (inter-quartile range). Asterisk denotes P<0.05 (significant) during inter-group comparision

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No difference was observed in the postoperative pain as assessed by VAS at all the time (P > 0.05). Neither was there any side effect related to amikacin in any of the patients studied.


   Discussion Top


The incidence of CRBD was reduced in the amikacin group from 66% observed in the control group to 44% (P < 0.05). Similarly, reduction in the severity of CRBD (moderate) was observed at 1 h in the amikacin group (P < 0.05). At rest of the time points, there was no difference in the severity of CRBD between the two groups (P > 0.05).

The urinary bladder receives cholinergic innervation by the pelvic nerves and adrenergic innervations by the hypogastric nerve. Contraction of the bladder, voluntary or involuntary, involves detrusor activity, mediated by stimulation of the muscarinic receptors by acetylcholine, released from activated cholinergic nerves.[2],[9] Overactivity of the bladder during filling/storage can be expressed as phasic involuntary contractions, as low compliance, or as a combination. Involuntary contractions are most commonly seen in association with neurologic disease (such as Parkinson's disease and multiple sclerosis), spinal cord injury, and diabetes; however, they may be associated with increased afferent input related to inflammation or irritation of the bladder or urethral wall, bladder outlet obstruction, stress urinary incontinence (perhaps because of sudden entry of urine into the proximal urethra), or aging (probably related to neural degeneration) or may be idiopathic.[18]

Overactive bladders are characterized by the symptoms of urinary frequency and urgency, with or without urge incontinence. These symptoms result from involuntary contractions of the bladder mediated by muscarinic receptors.[3],[4] Although behavioral and surgical interventions may be used to treat overactive bladder, antimuscarinic therapy by suppressing involuntary bladder contractions has been the mainstay of treatment for overactive bladder for almost 30 years.[19],[20],[21] Muscarinic receptor antagonists such as oxybutynin, tolterodine, and ketamine are the basis of medical treatment for CRBD.[5],[7] Gabapentin has also been reported to be effective in preventing CRBD by modulating the afferent input from the bladder and the excitability of the sacral reflex center.[6] Tramadol also inhibits the detrusor activity by inhibition of Type-1 muscarinic (M1) and Type-3 muscarinic (M3) receptors [22],[23] and reports to be effective in reducing the incidence and severity of CRBD.[9]

Amikacin is an aminoglycoside antibiotic, with wide spectrum of activity and commonly used before various surgical procedures to prevent postoperative infections. We hereby wished to observe and report if at all amikacin had any affect what so ever on the incidence and severity of CRBD in patients who had received amikacin as prophylactic antibiotic in patients undergoing elective PCNL for renal and upper ureteric stone and were catheterized intraoperatively. Single IV infusion of amikacin 500 mg (7.5 mg/kg) over a period of 30 min in a normal adult produces a mean peak serum concentration of 38 µg/mL at the end of the infusion and levels of 24 µg/mL, 18 µg/mL, and 0.75 µg/mL at 30 min, 1 h, and 10 h postinfusion, respectively. Eighty-four percent of the administered dose was excreted in the urine in 9 h and about 94% within 24 h.[24] Amikacin can operate on the motor plate in two ways: By presynaptic competition with the calcium by its binding sites, which prevents their participation in the release of acetylcholine, and by blocking postsynaptic cholinergic receptors.[16]

IV ketamine in subhypnotic doses has also been identified as an effective treatment of CRBD.[7] Preemptive administration of IV ketamine (0.5 mg/kg) has also been found to reduce incidence and severity of CRBD.[8] Tramadol has been reported to be effective in reducing the incidence and severity of CRBD.[9] Butorphanol administered 45 min before extubation IV has been observed to reduce the incidence and severity of CRBD.[10] Pretreatment with intravesical resiniferatoxin has been reported to significantly reduce the incidence and severity of CRBD in patients after TURP.[11] Intraoperative single-dose paracetamol was found to be effective in reducing the severity of CRBD and pain in urologic surgery.[12] Butylscopolamine 20 mg IV was also found to be an effective treatment modality for reducing severity of CRBD and the need for analgesics after recovery in patients undergoing urologic surgeries.[13] Pretreatment with pregabalin 150 mg orally before induction of anesthesia can also prevent CRBD.[14] Intraoperative dexmedetomidine administration decreased the incidence and severity of early postoperative CRBD in patients undergoing TURB.[15]

The symptoms due to surgical pain, hypoxia, and symptoms of CRBD may coincide and overlap each other; therefore, attempt should be made to exclude them one by one at the time of assessment of CRBD.

Limitation of our study is that we have evaluated the response of a single dose of amikacin on CRBD in patients undergoing urologic surgery. We also neither evaluated the dose-response titration nor evaluated the effect of continuing the therapy in the postoperative period. Another limitation was that we had not evaluated its role in patients undergoing all types of surgical procedures, even in patients who are catheterized for other medical procedures not requiring any surgical intervention. Further studies in these areas are suggested.

Amikacin, an aminoglycoside antibiotic, with wide spectrum of activity is commonly used before various urological and surgical procedures. Administration of single IV infusion of amikacin 500 mg over a period of 30 min in a normal adult as prophylaxis preoperatively reduces the incidence and severity of CRBD. We therefore suggest large multicenter studies to explore this aspect in greater detail and hope that prophylactic IV infusion of amikacin may establish itself as a modality for prevention of CRBD.


   Conclusion Top


Amikacin when given preoperatively significantly reduces the incidence and severity of catheter related bladder discomfort. It can be used safely without side effect. Further studies should be done to prove its efficacy.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
   References Top

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