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Hypobaric Spinal Anesthesia with Ropivacaine Plus Sufentanil for Traumatic Femoral Neck Surgery in the Elderly: A Dose-Response Study

Lilot, Marc MD*; Meuret, Pascal MD*; Bouvet, Lionel MD*; Caruso, Liana MD*; Dabouz, Rabia MD*; Deléat-Besson, Robert MD*; Rousselet, Bernard MD*; Thouverez, Bruno MD*; Zadam, Abbès MD*; Allaouchiche, Bernard MD, PhD*†; Boselli, Emmanuel MD, PhD*†

doi: 10.1213/ANE.0b013e31828f29f8
Regional Anesthesia: Research Report

BACKGROUND: In this randomized, prospective trial, we sought to determine the effective dose of hypobaric ropivacaine with sufentanil providing 95% success (ED95) in spinal anesthesia for traumatic femoral neck surgery in the elderly.

METHODS: Sixty-eight elderly patients with unilateral hip fracture randomly received 6, 8, 10, or 12 mg spinal hypobaric ropivacaine combined with 5 µg sufentanil. Patients remained in a lateral position for 15 minutes after spinal injection. The dose was considered successful if a unilateral sensory block >T12 was achieved, and there was no need for additional analgesia or conversion to general anesthesia. The ED95 was determined using logit analysis. The incidence of severe and very severe hypotension (systolic blood pressure decrease by >30% and >40% baseline, respectively) and the use of remifentanil were compared among groups using χ2 test for trend.

RESULTS: Three patients were excluded because of failure to reach the subarachnoid space. No differences in baseline demographic data were observed among groups. The ED95 for hypobaric ropivacaine was determined to be 9 mg (95% confidence interval, 8–14). Increasing doses of ropivacaine (6, 8, 10, and 12 mg) demonstrated a positive trend with respect to incidence of hypotension (53%, 47%, 87%, and 81%, P = 0.0004) and a negative trend with respect to the use of remifentanil (41%, 12%, 0%, and 0%, P = 0.0004). A significant difference in the level of sensory block (P < 0.0001) was observed among operative and nonoperative sides but not among ropivacaine dosing groups (P = 0.16). No difference in motor blockade, incidence of very severe hypotension, total dose of ephedrine, duration of surgery, patient satisfaction, operating conditions, or surgeon satisfaction scores was observed among groups. No cases of bradycardia were observed. No patient had a preoperative sensory level <T12 after 15 minutes in the lateral decubitus position, and no cases were converted to general anesthesia. There was no difference in undesirable outcomes or postoperative troponin values among groups.

CONCLUSIONS: The effective dose of hypobaric ropivacaine combined with sufentanil 5 µg providing 95% success in spinal anesthesia for traumatic femoral neck surgery in the elderly is ED95 = 9 mg (95% confidence interval, 8–14). Using doses exceeding the ED95 may increase the incidence of hypotension. If doses less than the ED95 are chosen, the use of additional analgesia may be necessary.

Published ahead of print April 16, 2013 Supplemental Digital Content is available in the text.

From the *Department of Anesthesiology and Intensive Care, Édouard Herriot hospital, HCL, Lyon, France; and Université Claude Bernard Lyon I University, University of Lyon, Lyon, France.

Accepted for publication February 7, 2013

Published ahead of print April 16, 2013

Funding: Financial support was obtained solely from departmental sources.

The authors declare no conflicts of interest.

This work was presented at the American Society of Anesthesiologists Annual Meeting 2011, Chicago, IL (Abstract A0607), and French Society of Anesthesiology and Intensive Care Annual Meeting 2011, Paris, France (Abstract R013).

Reprints will not be available from the authors.

Address correspondence to Emmanuel Boselli, MD, PhD, Service d’anesthésie-réanimation, Hôpital Édouard Herriot, 5 place d’Arsonval, 69003 Lyon, France. Address e-mail to emmanuel.boselli@chu-lyon.fr.

Many anesthesiologists consider spinal anesthesia to be the technique of choice, particularly in the elderly, frail patient.1,2 Recently, Neuman et al.3 showed lower odds of inpatient mortality and pulmonary complications in patients with regional anesthesia compared with general anesthesia, in a retrospective cohort of 18,000 patients operated for hip fracture surgery.

Elderly patients are more subject to hypotension with an increasing degree of sympathetic blockade as their vascular compensation mechanisms are often reduced.4 Hypobaric spinal anesthesia is a simple technique, which produces satisfactory operative conditions while minimizing hemodynamic change in the elderly population.5,6 The reduction of local anesthetic dose, and therefore, sympathectomy should contribute to more favorable hemodynamics and theoretically better outcomes in the elderly population. Low doses of local anesthetic have been studied for spinal anesthesia in patients older than 70 years with hip fracture. Five milligrams of hypobaric bupivacaine was found to be effective in preventing hemodynamic instability.5,7 The effective doses of plain spinal ropivacaine providing 50% (ED50) and 95% (ED95) success during lower limb surgery in adult patients have also been reported (7.6 and 11.4 mg, respectively).8 However, ropivacaine has never been studied in hypobaric spinal anesthesia in elderly patients. The primary aim of this trial was to determine the ED95 of hypobaric ropivacaine in spinal anesthesia for traumatic femoral neck surgery in patients older than 70 years.

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METHODS

The IRB (Comité de Protection des Personnes Sud-Est IV, study identifier CPP 09/003) and the National French Health Products Safety Agency (Agence Nationale de Sécurité du Médicament) approved the study protocol. This prospective, comparative, randomized, and single-blinded trial was prospectively registered at ClinicalTrials.gov (NCT01005550) and conducted from April 2009 to July 2011. Inclusion criteria were 70 years of age and older, ASA physical status I to III E, and mini-mental state examination (MMSE) score >24 undergoing emergent traumatic hip surgery in the dorsal supine position.9 Exclusion criteria were general contraindications for spinal anesthesia, effective peripheral nerve block at the time of anesthesia, and clopidogrel taken within 5 days before surgery. All participants provided written, informed consent before any study procedures.

The management of these patients did not differ from usual care. Preoperative analgesia consisted of IV acetaminophen 1 g, nefopam 20 mg every 6 hours, and subcutaneous morphine 5 mg every 6 hours if the 0 to 10 visual analog pain scale was >3. Two liters per day of IV glucose 5% saline solution was administered preoperatively. Patients received heparin calcium twice a day subcutaneously as preoperative thromboprophylaxis interrupted 12 hours before surgery. Patients with concomitant urinary tract infection were treated with oral norfloxacine, and surgery was delayed for 48 hours.

Patient randomization was established using computer-generated codes. Allocation concealment was accomplished by placing the randomization sequence in consecutively numbered, opaque envelopes. Each envelope contained a paper revealing the study dose of ropivacaine (6, 8, 10, or 12 mg) to be administered.

After placement of standard monitors, all patients received 5 mL/kg of IV 6% hydroxyethyl starch 130/0.4 over 15 minutes (Fig. 1). The initial systolic blood pressure (SBP) was then measured as the reference value. With the operative table horizontal, patients were placed in the lateral decubitus position with the operative hip up. Hypobaric rather than hyperbaric spinal anesthesia was chosen to avoid the fractured femoral neck to be placed dependent, which might have been painful for the patient. The hypobaric anesthetic solution was prepared as follows: 6, 8, 10, or 12 mg of plain 0.5% ropivacaine was diluted with 1 mL of sterile water and added to 1 mL of sufentanil 5 µg/mL.

Figure 1

Figure 1

The subarachnoid block was performed at the L4-L5 or L3-L4 interspace with a 25-gauge Quincke needle (Vygon®, Ecouen, France) using midline approach. If difficulty was encountered, a different interspace and/or a paramedian approach were used. After dural puncture, the needle aperture was oriented toward the operative side, and the anesthetic solution was injected slowly to provide “unilateral” block.10 Patients remained for 15 minutes in a lateral position and were then placed in the dorsal supine horizontal position for surgery. Since the provider of spinal anesthesia was not effectively blinded to group allocation because the volume of anesthetic solution varied with the dose, this provider left the operating room and a blinded second anesthesiologist measured and recorded all the patients’ variables during the protocol. Noninvasive automated arterial blood pressure and heart rate measurements were recorded just before spinal anesthesia (baseline), every 3 minutes up to 30 minutes and then every 5 minutes until 120 minutes. Severe and very severe hypotension were defined respectively as a decrease by >30% and 40% from baseline SBP. SBP <100 mm Hg or very severe hypotension was treated with IV boluses of ephedrine 6 mg. Bradycardia was defined as heart rate ≤45 bpm and was treated with an IV bolus of atropine 0.5 mg. Failure of spinal anesthesia was defined as failure to find the subarachnoid space or a < T12 sensory level as measured by pinprick test after 15 minutes. Insufficient block was defined as subjective pain expressed by the patient during surgery. The level of sensory blockade was assessed with an ice-cold alcohol-immersed sponge and pinprick test bilaterally 15 minutes after injection. The modified Bromage scale was used to assess motor blockade bilaterally at 15 minutes.11,12 In case of failure of spinal anesthesia, general anesthesia was performed. In case of insufficient block, remifentanil was administered using total IV analgesia (Minto model, Orchestra® Base Primea, Fresenius Vial SAS, Brézins, France). If a maximum cerebral concentration of 4 ng/mL was not sufficient, general anesthesia was performed. During surgery, each patient received 4 mL/kg/h of lactated Ringer’s solution IV. Blood loss volume was estimated and compensated by the same volume of 6% hydroxyethyl starch 130/0.4. The duration of sensory and motor blockade, duration of surgery, use of complementary analgesia, rate of hypotension, ephedrine consumption, patient visual analog pain scale in the postanesthesia care unit, patient and surgeon satisfaction, surgery conditions (excellent, good, fair, or poor), and increase of troponin values within the 3 first postoperative days were recorded. Undesirable outcomes such as red blood cells transfusion, acute urinary retention, renal dysfunction, cardiac infarction, cardiac dysfunction, stroke, deep venous thrombosis, pulmonary embolism, pneumonia, mental confusion, and death were recorded during the first 3 postoperative days.

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Statistical Analysis

Using a Cochran–Armitage test for trend in proportions, a sample size of 17 patients per group was obtained based on 4 groups with ropivacaine dosage values of 6, 8, 10, 12 mg and proportions of success equal to 0.5, 0.6, 0.8, and 0.9, respectively.13 A total sample size of 68 subjects with equally spaced x values provides 81% power to detect a linear trend using a 2-sided Z-test with continuity correction and a significance level of 0.05 (PASS® 8.0.05; NCSS, LCC, Kaysville, UT).14 Logistic regression based on “success” or “failure” for each patient was performed using SPSS version 12.0 (SPSS®, Chicago, IL). The ED95 of hypobaric spinal ropivacaine was calculated with corresponding 95% confidence interval (CI) using logit analysis.

Quantitative data were expressed in mean ± SD or median [interquartile] depending on their distribution (Kolmogorov-Smirnov test with Lilliefors correction). Qualitative data were expressed as n (%). Qualitative data were analyzed by χ2 test and quantitative data by Student t test if the distribution was normal or Mann-Whitney U test if the distribution was not normal. The incidence of hypotension and the use of remifentanil were compared using Cochran–Armitage test for trend. Durations of surgery and of sensory and motor blockade were compared with Kruskall-Wallis test. Sensory levels for both sides were compared with a 2-way analysis of variance (Statistica® 8.0, Statsoft, Tulsa, OK) using Bonferroni test for post hoc analysis. The 95% Bonferroni corrected CI were calculated using Minitab® 16.2.3 Statistical Software (Minitab Inc., State College, PA). The level of significance was set at P < 0.05.

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RESULTS

No differences in baseline demographic data were observed among groups (Table 1). Three patients were excluded because of failure to reach the subarachnoid space. No patient had a preoperative sensory level <T12 after 15 minutes of lateral decubitus. Additional analgesia by continuous IV remifentanil showed a negative trend among groups (Table 2). No conversion to general anesthesia was performed.

Table 1

Table 1

Table 2

Table 2

A positive trend was observed in the proportion of success among groups (Table 2). The dose-effect curve was plotted, showing the ED95 of hypobaric ropivacaine combined with 5 µg sufentanil to be 9 mg [8–14] (Fig. 2).

Figure 2

Figure 2

No differences were observed in duration of surgery, duration of motor blockade, patient satisfaction, operating conditions, or surgeon satisfaction scores (Table 2 and Fig. 3). A global difference was observed in the duration of sensory blocks, but no difference was observed among groups in post hoc analysis (Fig. 3). The lower quartile of sensory blockade duration time was superior to the upper quartile of surgery duration (Fig. 3). A significant difference in the level of sensory block (P < 0.0001) was observed among operative and nonoperative sides but not among ropivacaine dosing groups (P = 0.16). No difference was observed in motor blockade among groups (Fig. 4). A positive trend among the dose of hypobaric ropivacaine and the incidence of severe hypotension was observed (Table 2). There was no difference among groups in the incidence of very severe hypotension (SBP decrease by >40% baseline), total dose of ephedrine, undesirable outcomes, or postoperative troponin values. No cases of bradycardia were observed.

Figure 3

Figure 3

Figure 4

Figure 4

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DISCUSSION

This is the first study determining the ED95 of ropivacaine combined with 5 µg sufentanil for hypobaric spinal anesthesia in elderly patients undergoing traumatic hip fracture surgery. The ED50 of isobaric plain ropivacaine for total hip replacement in younger patients has been determined to be 12.8 mg.15 More recent data in adult patients provided an ED50 of 7.6 mg and ED95 of 11.4 mg for spinal plain ropivacaine in lower limb surgery of ≤50 minutes duration. These differences might be explained by the use of plain ropivacaine and by the fact that patients were younger than in the current study.

In 3 patients (4.4%), spinal anesthesia failed due to inability to reach the subarachnoid space. This rate is superior to the recently published rate of 0.04% (13 failed punctures among 35,960 procedures over 20 years).16 The explanation for this difference is contextual: hip fracture in elderly patients presents technical challenges to successful placement of spinal anesthesia.

The baricity of each of the solutions used in our study was slightly different: 1.2 to 2.4 mL of 5 mg/mL ropivacaine diluted in 3.2 to 4.4 mL of solution. However, the local anesthetic solution baricity has not been shown to significantly influence the level of anesthetic blockade in supine position.17–19 Ben-David et al.17 reported that for the same volume of bupivacaine, the maximum level of anesthetic blockade was similar at different concentrations but the intensity and time to regression were shorter with lower doses. On the contrary, use of high doses of hypobaric bupivacaine in a high volume of solution produces a deep bilateral spinal blockade.20

The goal when using unilateral spinal anesthesia versus bilateral conventional spinal anesthesia is to limit the sympathetic blockade to only 1 corporal side to reduce the hemodynamic impact.6 While unilateral blockade is often observed with a hyperbaric solution, a hypobaric solution is more likely to become bilateral.21 Nevertheless, the bilateral extension of the sensory and/or motor blockade does not induce hemodynamic disturbance because sympathetic blockade remains more unilateral.5,22 In the current study, variability in sensory and motor blockade level was observed both in the operative and nonoperative side.

A positive trend was observed among the dose of hypobaric ropivacaine and the incidence of severe hypotension (SBP decrease by >30% baseline). Moreover, the sympathetic blockade is shallower with unilateral compared with bilateral spinal anesthesia.23–25 The optimization of the hypobaric dose of local anesthetic is an objective for individual prevention of the hemodynamic disturbance26 caused by the decrease of systemic vascular resistance.4

Our study, however, presents some limitations. First, the lowest dosing group is above the estimated ED50, which might make this estimate inaccurate. Moreover, logit analysis is prone to bias in estimates and may narrow CIs.27 Furthermore, the test used for sample size calculation requires preassigned fixed scores and is more powerful when the scores and the binomial proportions have a similar shape, which is a priori unknown.13 Second, the baricity of the end solution was not measured and varied with the dose, which might have induced variability in the results. Another theoretical limit of this study is the relative long period of inclusion. Elderly patients admitted in the context of traumatic hip fracture frequently present with cognitive impairment or dementia, which may be detected using the MMSE.9 We decided to include only patients with MMSE >24 to protect patients’ ability to consent as well as to collect more reliable effectiveness data. This inclusion criterion, in part, explains the duration of the study. Nevertheless, we did not detect significant changes in the anesthetics and surgical management during investigation.

In conclusion, the dose of 0.5% plain ropivacaine combined with sufentanil 5 µg and rendered hypobaric by 1 mL of sterile water providing 95% success in spinal anesthesia for traumatic femoral neck surgery in the elderly is ED95 = 9 mg (95% CI, 8–14). Using doses exceeding the ED95 may increase the incidence of hypotension. If doses less than the ED95 are chosen, the use of additional analgesia might be necessary. Further study is needed to determine the impact of unilateral spinal anesthesia with hypobaric ropivacaine on outcome in elderly patients undergoing hip fracture surgery.

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DISCLOSURES

Name: Marc Lilot, MD.

Contribution: This author collected data and prepared the manuscript.

Attestation: Marc Lilot approved the final manuscript.

Name: Pascal Meuret, MD.

Contribution: This author designed the study, collected data, and helped prepare the manuscript.

Attestation: Pascal Meuret approved the final manuscript.

Name: Lionel Bouvet, MD.

Contribution: This author collected data and helped prepare the manuscript.

Attestation: Lionel Bouvet approved the final manuscript and attests to the integrity of the original data and the analysis reported in this manuscript.

Name: Liana Caruso, MD.

Contribution: This author collected data and helped prepare the manuscript.

Attestation: Liana Caruso approved the final manuscript and attests to the integrity of the original data and the analysis reported in this manuscript.

Name: Rabia Dabouz, MD.

Contribution: This author collected data and helped prepare the manuscript.

Attestation: Rabia Dabouz approved the final manuscript and attests to the integrity of the original data and the analysis reported in this manuscript.

Name: Robert Deléat-Besson, MD.

Contribution: This author collected data and helped prepare the manuscript.

Attestation: Robert Deléat-Besson approved the final manuscript and attests to the integrity of the original data and the analysis reported in this manuscript.

Name: Bernard Rousselet, MD.

Contribution: This author collected data and helped prepare the manuscript.

Attestation: Bernard Rousselet approved the final manuscript and attests to the integrity of the original data and the analysis reported in this manuscript.

Name: Bruno Thouverez, MD.

Contribution: This author collected data and helped prepare the manuscript.

Attestation: Bruno Thouverez approved the final manuscript and attests to the integrity of the original data and the analysis reported in this manuscript.

Name: Abbès Zadam, MD.

Contribution: This author collected data and helped prepare the manuscript.

Attestation: Abbès Zadam approved the final manuscript and attests to the integrity of the original data and the analysis reported in this manuscript.

Name: Bernard Allaouchiche, MD, PhD.

Contribution: This author helped design the study and prepare the manuscript.

Attestation: Bernard Allaouchiche approved the final manuscript, attests to the integrity of the original data and the analysis reported in this manuscript, and is the archival authors.

Name: Emmanuel Boselli, MD, PhD.

Contribution: This author designed and conducted the study, analyzed data, and prepared the manuscript.

Attestation: Emmanuel Boselli approved the final manuscript.

This manuscript was handled by: Terese T. Horlocker, MD.

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ACKNOWLEDGMENTS

The authors wish to thank Dr. Darren Raphael (Department of Anesthesiology and Perioperative Care, University of California, Irvine, CA) for his help in the English edition of the manuscript.

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