Effect of Ondansetron on the Incidence of Spinal Anaesthesia-Induced Hypotension in Elderly Patients Undergoing Fracture Hip Surgery
Effect of Ondansetron on the Incidence of Spinal Anaesthesia-Induced Hypotension in Elderly Patients Undergoing Fracture Hip Surgery: A Randomized, Double-Blind, Controlled Clinical Trial
This study aims to compare prophylactic intravenous ondansetron 4 mg versus placebo regarding the incidence of spinal anaesthesia-induced hypotension, defined as mean arterial pressure (MAP) fall >20% from baseline or systolic blood pressure (SBP) <90 mmHg/fall >20% from baseline, in elderly patients undergoing fracture hip surgery. The hypothesis is that a significant difference exists.
調査の概要
状態
状態
条件
条件
介入・治療
介入・治療
詳細な説明
Spinal anesthesia is widely used for fracture hip surgery because it provides effective surgical anesthesia while avoiding many physiological effects associated with general anesthesia. However, spinal anesthesia-induced hypotension (SIH), defined as a mean arterial pressure (MAP) decrease >20% from baseline or systolic blood pressure (SBP) <90 mmHg or a >20% decrease from baseline, is one of its most common complications. It primarily results from sympathetic blockade, causing vasodilation, reduced venous return, decreased cardiac output, and subsequent arterial hypotension. This may be particularly significant in elderly patients because of reduced cardiovascular, arterial, and autonomic reserve, together with a higher prevalence of cardiovascular disease and polypharmacy.
A sudden reduction in left-ventricular preload may activate cardiac mechanoreceptors and trigger the Bezold-Jarisch reflex (BJR). Serotonin-sensitive 5-HT3 receptors located on intracardiac vagal nerve endings may enhance vagal activity, contributing to bradycardia defined as heart rate (HR) < 50 beat per minute (bpm) and hypotension.
Ondansetron, a selective 5-HT3 receptor antagonist widely used as an antiemetic, has been investigated to attenuate the BJR and reduce SIH. Several randomized trials and meta-analyses have reported that prophylactic intravenous ondansetron, commonly given at 4-8 mg shortly before spinal injection, reduces post-spinal hypotension, bradycardia, and rescue vasopressor requirements, including in elderly surgical patients. An exploratory analysis suggested a greater preventive effect in patients aged ≥65 years.
However, the elderly subgroup was small and a 8 mg dose was used, leaving uncertainty regarding the optimal dose.
Spinal anesthesia technique The conduct of spinal anesthesia will be standardized across the two groups. On arrival to the operating room, standard ASA monitors including a pulse oximetry, electrocardiography and non-invasive blood pressure will be applied and the patients will be continuously monitored.
Baseline hemodynamics will be recorded at one, three, and five minutes before the studied drug administration, and the average will be taken as a baseline.
After an intravenous (IV) access is secured, all patients will receive an intraoperative infusion of 5-10 ml/kg Ringer's lactate or Normal saline solution per hour.
With the parturient in a sitting position, spinal anaesthesia will be conducted using the midline or paramedian approach after proper antiseptic cleaning and draping in the lumbar vertebral interspace of L3-L4 or a level below using a 25 or 22-gauge Quincke needle. After confirming free flow of cerebrospinal fluid, a 3 mL of hyperbaric bupivacaine 0.5% will be injected intrathecal in both Groups the same dose, Then all patients will be then made to lie supine.
Block-level will be tested every five minutes using a frozen plastic ampule of sterile water along the midclavicular line to check the response to cold, and the highest sensory level obtained will be registered.
Motor level will be assessed every five minutes using the Modified Bromage Scale, where Grade 0 indicates full movement of the hip, knee, and ankle; Grade 1 indicates inability to raise the extended leg while retaining the ability to flex the knee and move the ankle; Grade 2 indicates inability to flex the knee while retaining ankle movement; and Grade 3 indicates complete motor block with inability to move the hip, knee, or ankle. The highest Modified Bromage grade obtained will be recorded.
Surgeons will be allowed to proceed with surgery after attaining a block level of at least up to T10.
Data collection
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Patient characteristics including, age, sex, weight, height, and ASA status.
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Hemodynamic parameters including heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and oxygen saturation (SpO2) will be recorded at the following time points:
- Before injection of the study drug (baseline);
- At interval of 0 (baseline) and 5 minutes after the study drug administration and before intrathecal injection;
- At two-minutes intervals up to 20 minutes after intrathecal injection,
- Every 5 minutes until end of surgery.
- Postoperative hemodynamics at 2, 4, 6, 8, 12, 24 hours after surgery.
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Bradycardia (HR <50 bpm) will be treated with atropine 0.5 mg. Clinically significant hypotension, defined as MAP fall > 20% from baseline, or systolic blood pressure < 90 mmHg / fall > 20% from baseline, and if developed will be treated with IV ephedrine sulfate boluses of 6 mg as required. Amount of atropine and ephedrine required, sensory level achieved at 15 min of Spinal anaesthesia.
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Duration of surgery (minutes), total fluid intake (ml), and length of PACU stay (minutes).
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Side effects including hypotension (defined as MAP fall > 20% from baseline, or systolic blood pressure < 90 mmHg / fall > 20% from baseline), hypertension, bradycardia (HR < 50 bpm), tachycardia (HR > 100 bpm), hypoxemia (defined as a SpO2 level of less than 94% with a need for oxygen supplementation), respiratory depression, hallucinations, nystagmus, postoperative nausea and vomiting (PONV), and shivering will be treated and recorded.
The incidence of postoperative nausea and vomiting (PONV) episodes will be assessed in the first 24 h (at 2, 4, 6, 8, 12, 24 hours after surgery).
Patients who will develop shivering will be warmed with heated blankets.
研究の種類
研究の種類
入学 (推定)
入学
段階
段階
- フェーズ 4
連絡先と場所
研究連絡先
研究連絡先
- 名前:Mina Nagy Shoukrallah, M.B.B.Ch.
- 電話番号:+201271107782
- メール:menanagy396@gmail.com
研究場所
-
-
-
Asyut、エジプト
- Assiut University
-
-
参加基準
適格基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
- Age ≥ 65 years
- American Society of Anesthesiologists (ASA) physical status I, II, III (according to the American Society of Anesthesiologists classification).
- Scheduled for elective hip fracture surgery under spinal anaesthesia.
Exclusion Criteria:
- Patient refusal or inability to provide informed consent.
- Contraindication to spinal/neuraxial anaesthesia (coagulopathy, local infection at injection site, patient refusal, severe spinal deformity).
- Known hypersensitivity or contraindication to ondansetron (e.g., congenital long-QT syndrome).
- Baseline cardiac arrhythmia, significant conduction abnormality, or QTc > 450-470 ms on preoperative ECG.
- Severe cardiovascular disease (decompensated heart failure, recent myocardial infarction, severe valvular disease), ASA IV-V.
- Baseline bradycardia (heart rate < 50 bpm) or use of a permanent pacemaker.
- Concurrent use of medications that significantly affect heart rate or QT interval (e.g., class III antiarrhythmics), or of another 5-HT3 antagonist within 24 hours.
- Emergency surgery, or planned combined spinal-general anaesthesia/conversion anticipated.
- Pregnancy (not applicable in most cases given the population) and cognitive impairment precluding valid consent or symptom reporting.
研究計画
研究はどのように設計されていますか?
デザインの詳細
- 主な目的:防止
- 割り当て:ランダム化
- 介入モデル:並列代入
- マスキング:4倍
アーム数
武器と介入
参加者グループ / アーム参加者グループ / アーム |
介入・治療介入・治療 |
|---|---|
|
実験的:Group O (Ondansetron)
Ondansetron 4 mg diluted in 10 mL 0.9% normal saline over 60-90 seconds prior to spinal injection |
4 mg diluted in 10 mL 0.9% normal saline. |
|
プラセボコンパレーター:Group P (Placebo)
IV bolus of 10 mL 0.9% normal saline over 60-90 seconds prior to spinal injection |
10 mL IV 0.9% normal saline |
この研究は何を測定していますか?
主要な結果の測定
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Effect of prophylactic intravenous ondansetron versus Placebo on the incidence of spinal anaesthesia-induced hypotension
時間枠:From induction of spinal anaesthesia until completion of surgery.
|
Compare the effect of prophylactic intravenous ondansetron 4 mg versus Placebo on the incidence of spinal anaesthesia-induced hypotension, defined as MAP fall > 20% from baseline, or systolic blood pressure < 90 mmHg / fall > 20% from baseline, in elderly patients undergoing fracture hip surgery under spinal anaesthesia. |
From induction of spinal anaesthesia until completion of surgery.
|
二次結果の測定
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
The incidence of severe hypotension
時間枠:From induction of spinal anaesthesia until completion of surgery.
|
Severe hypotension, defined as systolic blood pressure (SBP) dropping to <60% of baseline |
From induction of spinal anaesthesia until completion of surgery.
|
|
The number of episodes of intraoperative hypotension.
時間枠:From induction of spinal anaesthesia until completion of surgery.
|
The percentage of people who experience hypotension, defined as MAP fall > 20% from baseline, or systolic blood pressure < 90 mmHg / fall > 20% from baseline, intraoperatively |
From induction of spinal anaesthesia until completion of surgery.
|
|
The incidence of bradycardia
時間枠:From induction of spinal anaesthesia until completion of surgery.
|
The Percentage of people who experience Bradycardia, defined as heart rate (HR) <50 bpm, intraoperatively |
From induction of spinal anaesthesia until completion of surgery.
|
|
The total rescue vasopressor (ephedrine) and atropine requirements between groups
時間枠:From induction of spinal anaesthesia until completion of surgery.
|
Total dose of intraoperative ephedrine or atropine if hypotension or bradycardia occurs |
From induction of spinal anaesthesia until completion of surgery.
|
|
The incidence of postoperative nausea and vomiting (PONV)
時間枠:Up to 24 hours postoperatively
|
PONV was evaluated using the PONV grading scale in the post-anesthesia care unit (PACU) at 2, 4, 6, 8, 12, and 24 hours PONV will be assessed using a four-grade scale: Grade 0 indicates no PONV; Grade I indicates nausea without vomiting; Grade II indicates nausea with vomiting occurring fewer than three times per day; and Grade III indicates vomiting occurring three or more times per day. |
Up to 24 hours postoperatively
|
|
The incidence of intraoperative and postoperative shivering between groups
時間枠:From induction of spinal anaesthesia up to 24 hours postoperatively
|
Assess the presence of shivering intraoperatively and postoperatively |
From induction of spinal anaesthesia up to 24 hours postoperatively
|
|
Sensory block characteristics (onset and duration) between groups.
時間枠:From induction of spinal anaesthesia until completion of surgery.
|
Block-level will be tested every five minutes using a frozen plastic ampule of sterile water along the midclavicular line to check the response to cold, and the highest sensory level obtained will be recorded Surgeons will be allowed to proceed with surgery after attaining a block level of at least T10. |
From induction of spinal anaesthesia until completion of surgery.
|
|
Motor block characteristics (onset, Modified Bromage score, and duration) between groups.
時間枠:From induction of spinal anaesthesia until completion of surgery.
|
Motor level will be assessed every five minutes using the Modified Bromage Scale, where Grade 0 indicates full movement of the hip, knee, and ankle; Grade 1 indicates inability to raise the extended leg while retaining the ability to flex the knee and move the ankle; Grade 2 indicates inability to flex the knee while retaining ankle movement; and Grade 3 indicates complete motor block with inability to move the hip, knee, or ankle. The highest Modified Bromage grade obtained will be recorded. Surgeons will be allowed to proceed with surgery after attaining a block level of at least T10. |
From induction of spinal anaesthesia until completion of surgery.
|
協力者と研究者
捜査官
捜査官
- スタディチェア:Sherif Sayyed Abdelrahem, PhD、Assiut University
- スタディディレクター:Abdelrahman Hamdy Mohamed, PhD、Assiut University
出版物と役立つリンク
一般刊行物
- Marashi SM, Soltani-Omid S, Soltani Mohammadi S, Aghajani Y, Movafegh A. Comparing Two Different Doses of Intravenous Ondansetron With Placebo on Attenuation of Spinal-induced Hypotension and Shivering. Anesth Pain Med. 2014 Mar 18;4(2):e12055. doi: 10.5812/aapm.12055. eCollection 2014 May.
- Sahoo T, SenDasgupta C, Goswami A, Hazra A. Reduction in spinal-induced hypotension with ondansetron in parturients undergoing caesarean section: a double-blind randomised, placebo-controlled study. Int J Obstet Anesth. 2012 Jan;21(1):24-8. doi: 10.1016/j.ijoa.2011.08.002. Epub 2011 Nov 18.
- Tatikonda CM, Rajappa GC, Rath P, Abbas M, Madhapura VS, Gopal NV. Effect of Intravenous Ondansetron on Spinal Anesthesia-Induced Hypotension and Bradycardia: A Randomized Controlled Double-Blinded Study. Anesth Essays Res. 2019 Apr-Jun;13(2):340-346. doi: 10.4103/aer.AER_22_19.
- Mendonca FT, Crepaldi Junior LC, Gersanti RC, de Araujo KC. Effect of ondansetron on spinal anesthesia-induced hypotension in non-obstetric surgeries: a randomised, double-blind and placebo-controlled trial. Braz J Anesthesiol. 2021 May-Jun;71(3):233-240. doi: 10.1016/j.bjane.2020.12.028. Epub 2021 Mar 22.
- Hou XM, Chen YJ, Lai L, Liu K, Shen QH. Ondansetron Reduces the Incidence of Hypotension after Spinal Anaesthesia: A Systematic Review and Meta-Analysis. Pharmaceuticals (Basel). 2022 Dec 19;15(12):1588. doi: 10.3390/ph15121588.
- Mohamed SA, Hussam AM, Abdallah SA, Sarhan KA, Shaban AM. Ondansetron Is an Effective Alternative to Decrease the Incidence of Postspinal Hypotension in Healthy Subjects Undergoing Infra-Umbilical Surgeries Compared To Combined Volume Loading and Vasoconstrictors: Randomized Controlled Trial. Open Access Maced J Med Sci. 2018 Dec 19;6(12):2363-2368. doi: 10.3889/oamjms.2018.491. eCollection 2018 Dec 20.
- Abbas N, Shah SA, Naqvi SS. Role of prophylactic ondansetron for prevention of spinal anaesthesia induced hypotension in lower segment caesarean section. Pakistan Armed Forces Medical Journal. 2016 Dec 1(6):790. https://pafmj.org/index.php/PAFMJ/article/download/927/777
- Qin R, Xu X, Zhao N, Shi Y, Chen Y, Chen J, Ni X. Effect of different prophylactical doses of ondansetron for the hemodynamic stability in patients undergoing cesarean section: a randomized controlled study. Front Med (Lausanne). 2025 Apr 3;12:1495721. doi: 10.3389/fmed.2025.1495721. eCollection 2025.
- Xie F, Sun DF, Yang L, Sun ZL. Effect of anesthesia induction with butorphanol on postoperative nausea and vomiting: A randomized controlled trial. World J Clin Cases. 2023 Nov 16;11(32):7806-7813. doi: 10.12998/wjcc.v11.i32.7806.
- 8. Rashad MM, Farmawy MS. Effects of intravenous ondansetron and granisetron on hemodynamic changes and motor and sensory blockade induced by spinal anesthesia in parturients undergoing cesarean section. Egypt J Anaesth. 2013;29(4):369-374. doi:10.1016/j.egja.2013.04.004. Doi link https://doi.org/10.1016/j.egja.2013.04.004
- Owczuk R, Wenski W, Twardowski P, Dylczyk-Sommer A, Sawicka W, Wujtewicz MA, Marciniak A, Polak-Krzeminska A, Jasinski T, Wujtewicz M. Ondansetron attenuates the decrease in blood pressure due to spinal anesthesia in the elderly: a double blind, placebo-controlled study. Minerva Anestesiol. 2015 Jun;81(6):598-607.
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主要日程の研究
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研究開始
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研究の完了 (推定)
研究の完了
試験登録日
最初に提出
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QC基準を満たした最初の提出物
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最初の投稿 (実際)
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学習記録の更新
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QC基準を満たした最後の更新が送信されました
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- 04-2026-201911
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