Ropivacaine: Anesthetic consideration in elderly patients for transurethral resection of prostrate a clinical trial.

BACKGROUND: Ropivacaine has less systemic toxicity and greater differentiation of sensory and motor blockade after subarachnoid block. This study was aimed to evaluate the anesthetic efficacy of intrathecal 0.75% isobaric ropivacaine alone or with fentanyl in elderly patients undergoing transurethral resection of prostrate.
MATERIALS AND METHODS: Fifty four elderly consented patients of ASA grade I-III scheduled for transurethral resection of prostrate under the subarachnoid block were randomized to receive either intrathecal 4 mL of 0.75% isobaric ropivacaine (Group R, n = 27) or 3.5 mL of 0.75% isobaric ropivacaine with 0.5 mL (25 μg) of fentanyl (Group RF, n = 27). The characteristics of sensory and motor blockade, intraoperative hemodynamic changes, and secondary effects were noted for evaluation.
RESULTS: There was no significant difference in the demographic profile of patients. The surgical anesthesia was adequate for TURP surgery in all patients. The median time to achieve the sensory blockade at T10 dermatome was 3.2 ± 1.5 min in Group R and 3.5 ± 1.3 min in Group RF. The median duration of sensory blockade at T10 was 130.6 ± 10.2 min in Group R and 175.8 ± 8.6 min in Group RF. The median duration of complete motor block was significantly shorter than the duration of sensory blockade (P < 0.001). There were fewer episodes of manageable hypotension in 5 patients of Group R and 11 patients of Group RF. No secondary effects have occurred in any patients.
CONCLUSION: The intrathecal 0.75% isobaric ropivacaine alone or with fentanyl has provided effective surgical anesthesia for transurethral resection of prostrate and hemodynamic stability in elderly patients.

RCT Entities:   Population Interventions Outcomes

INTRODUCTION

Benign prostatic hypertrophy frequently leads to symptomatic bladder outlet obstruction in men older than 60 years. Aging and disease make elderly patients susceptible to hypotension during general anesthesia as these patients have a relatively high (3060%) prevalence of coexisting cardiovascular and pulmonary disorders. The clinical studies have demonstrated that transurethral resection of prostate (TURP) is considered a safe procedure than open prostatectomy in elderly patients under regional anesthesia as it allowed the observation of early symptoms and signs of TURP syndrome and also reduces the incidence of postoperative venous thrombosis.[1] Limited data have been published on the intrathecal use of ropivacaine for urological surgery.

Ropivacaine, an amide local anesthetic, shares many physiochemical properties with bupivacaine but has shown a safety profile over bupivacaine due to the reduced central nervous system and cardiac toxicity.[23] Ropivacaine has low lipid solubility; hence, it blocks nerve fibers involved in pain transmission to a greater degree than those controlling motor functions. It has shown wide clinical utility for a wide range of indications at different doses. Recent clinical data have shown that ropivacaine is clinically effective and safe for regional anesthetic techniques with good tolerability. Ropivacaine could provide adequate surgical anesthesia without compromising early ambulation and discharge.[4567]

The level of sensory blockade is required at T10 dermatome for the TURP procedure and duration of the procedures ranged between 60 and 75 min. The principal determinants of the extension and duration of the anesthetic block depend on the type and concentration of the local anesthetic used. Lipophilic opioids, as fentanyl or sufentanil, are increasingly being given intrathecally as adjuvant to local anesthetics to enhance sensory block without prolonging motor recovery.

This clinical study was designed to evaluate the clinical efficacy and safety of intrathecal 0.75% isobaric ropivacaine alone or with fentanyl for transurethral resection of prostrate (TURP) in elderly patients.

MATERIALS AND METHODS

This prospective blind randomized clinical study was conducted on 54 male adult patients of physical status ASA grade I-III, aged 55-75 years with body weight 65-95 kg and height 160-175 cm, scheduled for TURP under subarachnoid block, from May 2011 to April 2012. After approval of Institutional Ethical Committee and written informed consent, all patients were subjected to preanesthetic assessment. Patients with severe cardiac or pulmonary diseases, neurologic or renal dysfunction, bleeding or coagulation disorder, allergy to local anesthetic amides, deformed spinal column, infection at site of lumber puncture, or refusal to technique were excluded from the study. Before enrollment for the study, patients were explained on the method of sensory and motor assessments.

The patients were randomized, according to computer-generated number, into two treatment groups of 27 each to receive either an intrathecal injection of 4 mL of 0.75% isobaric ropivacaine (Group R, n = 27) or 3.5 mL of 0.75% isobaric ropivacaine with 0.5 mL (25 μg) of fentanyl (Group RF, n = 27). They were preloaded with lactated Ringer 10 mL/kg before the initiation of the subarachnoid block and standard monitors for heart rate, continuous ECG (lead II), continuous pulse oximetry, and non-invasive systemic blood pressure (SBP) were attached. The subarachnoid puncture was performed aseptically in the sitting position with a 25 G Whitacre needle by midline approach at the L2-3 or L3-4 interspace and one of the study drug was given over 30 s according to group allocation. The direction of the needle aperture was cranial during injection. To ensure blinding, the local anesthetic solutions were presented in identical numbered ampules. Immediately after intrathecal injection, patients were laid supine.

The onset and duration of sensory blockade with maximal cephalad spread, the onset, intensity, and duration of motor blockade were recorded at 1 and 2 min followed by at 2 min intervals till the surgical anesthesia was achieved at the dermatome level T10. The segmental level of sensory block to pin prick was evaluated bilaterally along the midclavicular line by using a short beveled 27-gauge needle. The motor block of both legs was assessed using the modified Bromage scale (0 = able to lift extended leg at hip: full movement, 1 = able to flex the knee but not able to raise the extended leg, 2 = unable to flex knee, 3 = unable to move foot: No movement). The surgical anesthesia was considered effective when at least the T10 dermatome was anesthetized. After adequate spinal block has been achieved, the time from the end of intrathecal injection to readiness for surgery was noted. Then, the patient was poisoned in the lithotomy position and surgery started.

Hemodynamic parameters of the heart rate, ECG, arterial blood pressure, and SpO2 were recorded before the intrathecal injection and thereafter at every 2 min during the first 10 min, and then every 5 min in the first hour and every 10 min until the patient was transferred to the post-anesthesia room. Intraoperatively the oxygen was administered at a rate of 3 L/min via a face mask.

Criteria for tachycardia, bradycardia, hypotension, and hypertension were any increase or decrease more than 20% from the baseline. The hypotension (SBP < 90 mmHg) was treated with intravenous boluses of mephentermine 6 mg and additional Ringer lactate solution and bradycardia (heart rate < 50 b/m) with intravenous atropine. Respiratory depression was defined when a respiratory rate is less than 8 breaths/min or oxygen saturation less than 90% on air. All patients were catheterized after surgery.

Postoperatively the sensory and motor assessments were continued at 30 min intervals until normal sensation returned. Other adverse effects of pruritis, nausea and vomiting, and shivering were recorded.

Statistical analysis

The sample size was based on initial pilot study which indicated that approximately 23 patients should be included in each group in order to detect a 30 min difference in the mean duration of motor blockade between the groups for type 1 error of 0.01 and power of 90%. Assuming a 5% dropout rate, the final sample size was set of 54 patients. Statistical analysis was done for comparing observed data by using Student's t test, chi square test, and Mann-Whitney U test, and P value of < 0.05 was considered statistically significant.

RESULTS

Fifty four elderly consented patients were randomized to the two treatment groups of 27 patients each. The demographic data were similar between the groups for age, weight, height, ASA classification as well as duration of surgery [Table 1]. All patients were able to co-operate fully with the subsequent assessments. There was no significant difference in the median time of onset of sensory blockade at the T10 dermatome which was 3.2 ± 1.5 min in the Group I (RF) and 3.5 ± 1.2 min in Group II (RF). The time taken to achieve maximum sensory block was 9.8 ± 3.2 min in Group I and 8.13 ± 1.92 min in Group II. The adequate level of sensory analgesia was achieved in all patients before surgery. The median duration of sensory blockade till complete regression was 267.03 ± 45.7 min in Group I and 351.28 ± 30.45 in Group II. Increase in the mean duration time in the fentanyl group was statistically highly significant (P < 0.001).

Table 1

Demographic profile of patients

The onset of motor blockade was comparable between groups with a median onset time to achieve a Bromage score of 3 being 14.2 ± 2.4 min in Group I and 11.4 ± 6.3 min in Group II. The complete motor blockade of both legs was observed in all patients. The median duration of complete motor blockade was 218.5 ± 45.7 min in Group I and 235.13 ± 26.8 min in Group II.

The duration of sensory blockade was statistically prolonged than motor blockade in both groups (267.03 ± 45.7 min versus 218.5 ± 45.7 in Group I and 351.28 ± 30.45 versus 235.13 ± 26.8 min in Group II) (P value < 0.05) [Table 2].

Table 2

Sensory and motor blockade profile of both groups

The quality of surgical anesthesia was comparable between the groups and all patients were successfully operated for TURP surgery and no patients required intra-operative supplemental analgesics.

Hemodynamic changes of systolic blood pressure and heart rate of both groups are shown in Table 3. An initial hypotension was observed in both groups but hypotension requiring treatment with vasopressor occurred in 5 (15%) patients of Group I and 11 (40%) patients of Group II. No significant difference was found between groups for SBP till end of surgery. Heart rate showed difference after 15 min between groups but significant bradycardia has not occurred in any patient. The quantity of intravenous fluid used during spinal anesthesia was similar between groups.

Table 3

Hemodynamic parameters of heart rate and systolic blood pressure (SBP)

The incidence of adverse effects of pruritis, nausea, vomiting, and shivering was comparable between two groups. No patients complained of any other neurological symptoms at the postoperative visit.

DISCUSSION

The present study was designed to compare the anesthetic efficacy and safety of intrathecal 0.75% isobaric ropivacaine alone or with 25 μg of fentanyl for transurethral resection of prostate in elderly patients. The study showed that intrathecal administration of ropivacaine alone or with intrathecal fentanyl has provided effective surgical anesthesia for TURP surgery with cardiovascular stability. Intrathecal ropivacaine with fentanyl has no effect on the onset of sensory analgesia but has improved the quality and duration of the sensory blockade without compromising early mobilization and discharge. The patients showed mild and short-lived sedation but no hemodynamic side effects. There were no transient neurological symptoms in either group.

We have done a dose finding pilot study for evaluating the minimum effective dose of 0.75% isobaric ropivacaine required for successful TURP surgery under spinal anesthesia in elderly patients as variability in lumbosacral cerebrospinal fluid volume affects the spread of spinal sensory anesthesia. The CSF volume cannot be readily predicted in elderly patients, as uncertainty in the extent and duration of spinal anesthesia is inevitable after intrathecal injection of a single local anesthetic dose.[8] Our pilot study and other clinical studies have shown that 3.5 mL of 0.75% isobaric ropivacaine has resulted in very variable extent of block and lower quality of intraoperative analgesia.[910] We believed that reduced dose of isobaric ropivacaine will not procure adequate surgical anesthesia. Thus, 4 mL of intrathecal volume of 0.75% isobaric ropivacaine was recommended for effective surgical anesthesia for TURP surgery either alone or with fentanyl.

The synergistic interaction between spinal opioids and local anesthetics is characterized by enhanced somatic analgesia without effect on the degree or level of the local anesthetic induced sympathetic or motor blockade.[1112] In the present study, 25 μg (0.5 mL) of fentanyl was added to 3.5 mL of 0.75% ropivacaine to avoid the possibility of failure of low dose ropivacaine, if used alone. The intrathecal fentanyl has intensified and accelerated the onset of sensory without increasing the intensity of motor block or prolonging recovery and early discharge. Kuusniemi et al. showed that adding 25 μg to 10 mg of bupivacaine compared to 10 mg of bupivacaine only will prolong the sensory block.[13]

Hypotension is common after subarachnoid administration of local anesthetics and episodes of hypotension can be detrimental to the elderly patient during endoscopic urological surgery. Critchley et al. reported that 69% of elderly patients required treatment for hypotension during spinal anesthesia.[14] In our study, only five patients required mephentermine along with bolus intravenous infusion in Group R and 11 patients in Group RF. No severe bradycardia occurred in the present study.

Intrathecal opioids may provide benefits in increasing depth of spinal anesthesia, but carry a risk of respiratory depression. The use of 25 μg of intrathecal fentanyl in non-premedicated elderly patients did not alter respiratory rate, end tidal CO2, minute ventilation, or the ventilatory response to CO2.[15] In our study, no respiratory depression has occurred.

Pruritis is the most common side effect observed with the use of intrathecal opioids. It may be generalized but may be localized to the face, neck, or upper thorax. The incidence varies widely and often elicited after questioning.[16] In the present study, only three patients complained of pruritis. It was well tolerated and none of the patients needed treatment.

Nausea and vomiting are unwanted side effects after spinal block with incidence of 18% for nausea and 7% for vomiting, as shown in the study of Carpenter et al.[16] In the present study, none of the patient has suffered from nausea or vomiting. Moreover, no patients have complained of postdural puncture headache.

CONCLUSION

Elderly patients require evidence-based strategies to reduce potential complications of TURP surgery and there are limited geriatric specific data to direct care of the elderly patients. The intrathecal 0.75% isobaric ropivacaine alone or with 25 μg fentanyl has provided clinically effective surgical anesthesia for TURP, with rapid return of motor function and less hemodynamic alterations. Early mobilization has accelerated the postoperative recovery.