Pain Control After Aortic EndoaneurYsmEctomy (POPEYE)

Postoperative Pain Clinical Trial

— POPEYE  

Official title:

Post-Operative Pain Control After Aortic EndoaneurYsmEctomy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06244732
• Other study ID #: POPEYE_CET 131-2023
• Status: Recruiting
• Phase: N/A
• Start date: February 19, 2024
• Est. completion date: March 2027

Study information

• Verified date: March 2024
• Source: IRCCS Policlinico S. Donato
• Contact: Mattia Ricotti
• Phone: +390252774236
• Email: mattia.ricotti[@]grupposandonato.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Open abdominal aortic aneurysm repair (OR-AAA) is an operation associated with high morbidity, and has 30-day mortality rates of between 4 and 14%. Post-operative pain management represents a primary anesthetic focus.

A better analgesia, in addition to being desirable for the patient, can potentially reduce complications associated with postoperative pain and ensure faster functional recovery.

The modern concept of multimodal analgesia involves the association of multiple drugs and/or analgesic techniques to maximize the quality of analgesia and reduce the side effects of the individual methods. In this context, the addition of epidural analgesia (EA) to the intravenous administration of "traditional" analgesic drugs has assumed the role of gold standard in many surgeries, including OR-AAA.

Over time, EA has proven to be a better analgesic technique than the use of intravenous opioids alone, however there is much uncertainty regarding its ability to reduce complications, morbidity and mortality of patients.

For some time, efforts to research effective, less invasive and safe anesthetic alternatives, have been directed towards the development of multimodal analgesia protocols with the aim of reducing complications and ensuring faster recovery. New approaches to post-operative pain management are emerging, including rectus sheat block (RSB).

Currently there is no evidence regarding the effectiveness of RSB in pain control after OR-AAA.

In this context, the study aims to compare two different post-operative pain management protocols, with the aim of verifying whether the use of RSB can guarantee a non-inferior level of analgesia with reduction of complications compared to AE.

Description:

This is a prospective, randomized controlled, single-centre, non-profit, spontaneous study, which involves the evaluation of the control of post-operative pain in a population of adult patients admitted to the General Intensive Care Unit after elective open endoaneurysmectomy of the abdominal aorta.

The study will be conducted by analyzing two groups of patients, randomized to receive ether postoperative analgesia via epidural catheter (EA Group) or repeated blocks of the rectus fascia (RSB Group).

Pre- and intra-operative management In EA Group the epidural catheter will be positioned, according to the normal practices of the Operating Unit, before the operation. The insertion of the catheter will be carried out at the T10-T12 level for a maximum of 5-7 cm in the epidural space.

For both groups under study, the operation will be conducted under balanced general anesthesia, using a volatile anesthetic (Desflurane or Sevoflurane) associated with Remifentanil, with titratable doses in order to guarantee an adequate depth of anesthesia, understood as bispectral index (BIS ) between 40 and 60. Myoresolution will be maintained with the use of neuromuscular monitoring (TOF, Train Of Four).

After intubation, the bladder catheter, nasogastric tube, central venous catheter (with ultrasound-guided technique) will be positioned and the following will be prepared:

• Cell saver for blood recovery

• Body temperature monitoring via throat probe

• Minimally invasive arterial hemodynamic monitoring with FloTrac system and continuous detection of the following parameters:

• Mean arterial pressure (MAP)

• Cardiac Index (CI)

• Stroke Volume Variation (SVV) These parameters, as usual, will guide the anesthetic conduct for the optimization of blood volume and intraoperative hemodynamic performance.

• Prophylaxis of nausea and vomiting will be carried out by administering Dexamethasone 4 mg to all patients at induction and Ondansetron 4 mg before extubation

• Upon closure of the abdominal muscle fascia, intravenous analgesia will be administered with Paracetamol 1 g, Ibuprofen 600 mg and MgSO4 2 g At the end of the surgical procedure, each patient, as usual and regardless of the study protocol, will be transferred to the General Intensive Care Unit, where monitoring and the subsequent recovery phase will continue.

Post-operative management All patients will be transferred to the General Intensive Care Unit with continued sedation and mechanical ventilation, in order to standardize the close monitoring of vital functions, the recovery phase and the management of the analgesia protocol.

Each patient will be eligible for awakening and extubation - and therefore for the start of the analgesia protocol - once all the following criteria have been met:

• Body temperature ≥ 35.5° C

• MAP ≥ 65 mmHg (with max basic norepinephrine dosage 0.1 mcg/kg/min)

• TOF-Ratio ≥ 0.9 If the conditions for awakening are not respected, the clinical conditions will be optimized in order to restore the stability necessary for extubation. Patients who have not reached the aforementioned criteria within 12 hours of admission to the ICU will exit the study protocol (see "drop-out criteria").

From the moment of awakening (T0), observation and data collection will continue in the Intensive Care Unit for a total of 36 hours.

Analgesia protocol

The administration of analgesia according to the usual protocols will begin before awakening in those patients who have met the criteria for extubation:

• Group EA will receive analgesia via epidural catheter (Ropivacaine 0.15% with double initial bolus and subsequent continuous infusion 5 ml/h via elastomeric pump)

• in the RSB Group, repeated blocks of the abdominal wall will be performed using special catheters positioned bilaterally in the rectus muscle fascia using ultrasound guidance (Ropivacaine 0.375% 20 ml per side, administered every 12 hours: at T0, T12 and T24) In addition, both groups will be administered intravenous analgesia at predetermined times: 1 g of paracetamol QID (quater in day, except for patients <50 kg and/or with risk factors for hepatotoxicity in which it will be administered in a total dose of 3 g/day), 600 mg of ibuprofen BID (bis in day) and 2 g of MgSO4 TID (tris in day).

Pain symptoms will be assessed according to the NRS scale. This system involves the direct evaluation by the patient of the degree of pain perceived on a scale ranging from 0 (no pain) to 10 (worst possible pain). In our study we will consider values greater than or equal to 4 to be unacceptable. In this case, rescue therapy with opioids is envisaged in addition to the intravenous therapy normally administered. The opioid of choice for our protocol is intravenous morphine, administered in boluses at a dosage of 2 mg, repeatable every 15 minutes (= max 8 mg in one hour) until pain symptoms improve with NRS<4 or appearance of side effects, considering a maximum daily dose of 50 mg.

Data collection

The following variables will be collected from the medical records, which will then be pseudonymised and inserted into a database to be adequately analysed:

1. Pre-operative:

1. Anthropometric parameters (age, sex, BMI)

2. ASA class

3. Revised Cardiac Risk Index

4. METS

5. Major comorbidities:

i) Diabetes mellitus (DM) ii) Ischemic heart disease (IC) iii) Heart failure (HFS) iv) Chronic obstructive pulmonary disease (COPD) v) Chronic kidney disease (CKD) vi) Other significant pathologies

2. Intra-operative:

a) Type of surgical procedure i) aortobisiliac repair (AO-BIS) ii) aorto-bifemoral repair (AO-BIF) iii) aorto-aortic (AO-AO) repair b) Surgical time c) Time and type of aortic clamping d) Hemodynamic parameters and events i) Maximum dosage of Norepinephrine (mcg/kg/min) ii) MAP ≤ 65 mmHg iii) FloTrac: CI ≤ 2 L/min and/or SVV > 13% iv) Water balance v) Total transfusions in ml (exogenous + blood recovery) vi) Intraoperative AAII thrombotic complications

3. Post-operative:

a) Pain (NRS scale) both at rest ("static") and upon coughing ("dynamic") i) upon awakening (T0) ii) 2, 4, 8, 12, 18, 24, 30, 36 hours after waking up b) Total dose of rescue opioid c) Occurrence of complications related to the operation and/or the patient's comorbidities i) Re-intervention ii) Thrombosis AAII iii) Hemorrhage iv) major cardiac complications (ACS, ACC, arrhythmias) v) infectious complications (wound infection, sepsis, septic shock) vi) pulmonary complications (pneumonia, respiratory failure, pulmonary edema) vii) acute renal failure d) Occurrence of complications related to the therapy administered i) Nausea/vomiting from opioid consumption ii) Failure of the analgesic technique (uncontrolled pain) iii) Hypotension treatable with max norepinephrine base 0.1 mcg/kg/min iv) Hypotension not treatable without higher doses of basic norepinephrine v) Paresthesia of lower limbs vi) Motor deficit of lower limbs vii) Other complications of AE: direct neurological damage, dural puncture headache, subarachnoid injection/spinal anesthesia, urinary retention, low back pain, epidural hematoma, infection, drug allergy, AL absorption viii) Other complications of RSB: infections, fascial hematoma, drug allergy, AL absorption The analysis continues for a total period of 36 hours after waking up in the Intensive Care Unit. The length of in-hospital stay will be also recorded.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: March 2027
• Est. primary completion date: February 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• adult patients (age > 18 years)

• patients who have given their consent to participate in the study

• patients undergoing elective "open" surgical treatment of an abdominal aortic aneurysm with a midline xipho-pubic incision.

Exclusion Criteria:

• Pregnant women

• Patients being treated for chronic pain

• Known allergy to drugs included in analgesia protocols

• Contraindications to the use of one of the two methods provided:

• refusal by the patient

• infection at the puncture site

• coagulopathy:

1. PTT > 40 s and/or INR > 1.4

2. platelet count < 50,000/µL

3. taking antiplatelet or anticoagulant drugs that have not been discontinued in good time, according to international guidelines

• Emergent intervention

• Lack of consent to participate in the study

Related Conditions & MeSH terms

• Abdominal Aortic Aneurysm
• Aneurysm
• Aortic Aneurysm
• Aortic Aneurysm, Abdominal
• Postoperative Pain

Intervention

Procedure:
• Postoperative pain control
Postoperative analgesia after OR-AAA

Locations

Country	Name	City	State
Italy	I.R.C.C.S. Policlinico San Donato	San Donato Milanese	Milan

Sponsors (1)

Lead Sponsor	Collaborator
IRCCS Policlinico S. Donato

Country where clinical trial is conducted

Italy, 

References & Publications (29)

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Bardia A, Sood A, Mahmood F, Orhurhu V, Mueller A, Montealegre-Gallegos M, Shnider MR, Ultee KH, Schermerhorn ML, Matyal R. Combined Epidural-General Anesthesia vs General Anesthesia Alone for Elective Abdominal Aortic Aneurysm Repair. JAMA Surg. 2016 Dec — View Citation

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Dobson SW, Weller RS, Edwards C, Turner JD, Jaffe JD, Reynolds JW, Henshaw DS. A randomized comparison of loss of resistance versus loss of resistance plus electrical stimulation: effect on success of thoracic epidural placement. BMC Anesthesiol. 2022 Feb — View Citation

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Greco KJ, Brovman EY, Nguyen LL, Urman RD. The Impact of Epidural Analgesia on Perioperative Morbidity or Mortality after Open Abdominal Aortic Aneurysm Repair. Ann Vasc Surg. 2020 Jul;66:44-53. doi: 10.1016/j.avsg.2019.10.054. Epub 2019 Oct 28. — View Citation

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Hakim SM, Narouze S, Shaker NN, Mahran MA. Risk factors for new-onset persistent low-back pain following nonobstetric surgery performed with epidural anesthesia. Reg Anesth Pain Med. 2012 Mar-Apr;37(2):175-82. doi: 10.1097/AAP.0b013e3182411048. — View Citation

Hicks CW, Wick EC, Canner JK, Black JH 3rd, Arhuidese I, Qazi U, Obeid T, Freischlag JA, Malas MB. Hospital-Level Factors Associated With Mortality After Endovascular and Open Abdominal Aortic Aneurysm Repair. JAMA Surg. 2015 Jul;150(7):632-6. doi: 10.100 — View Citation

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Kietaibl S, Ferrandis R, Godier A, Llau J, Lobo C, Macfarlane AJ, Schlimp CJ, Vandermeulen E, Volk T, von Heymann C, Wolmarans M, Afshari A. Regional anaesthesia in patients on antithrombotic drugs: Joint ESAIC/ESRA guidelines. Eur J Anaesthesiol. 2022 Fe — View Citation

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Monaco F, Pieri M, Barucco G, Karpatri V, Redaelli MB, De Luca M, Mattioli C, Bove T, Melissano G, Chiesa R, Landoni G, Zangrillo A. Epidural Analgesia in Open Thoraco-abdominal Aortic Aneurysm Repair. Eur J Vasc Endovasc Surg. 2019 Mar;57(3):360-367. doi — View Citation

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Park WY, Thompson JS, Lee KK. Effect of epidural anesthesia and analgesia on perioperative outcome: a randomized, controlled Veterans Affairs cooperative study. Ann Surg. 2001 Oct;234(4):560-9; discussion 569-71. doi: 10.1097/00000658-200110000-00015. — View Citation

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Salicath JH, Yeoh EC, Bennett MH. Epidural analgesia versus patient-controlled intravenous analgesia for pain following intra-abdominal surgery in adults. Cochrane Database Syst Rev. 2018 Aug 30;8(8):CD010434. doi: 10.1002/14651858.CD010434.pub2. — View Citation

Stenger M, Fabrin A, Schmidt H, Greisen J, Erik Mortensen P, Jakobsen CJ. High thoracic epidural analgesia as an adjunct to general anesthesia is associated with better outcome in low-to-moderate risk cardiac surgery patients. J Cardiothorac Vasc Anesth. — View Citation

Tran DQ, Van Zundert TC, Aliste J, Engsusophon P, Finlayson RJ. Primary Failure of Thoracic Epidural Analgesia in Training Centers: The Invisible Elephant? Reg Anesth Pain Med. 2016 May-Jun;41(3):309-13. doi: 10.1097/AAP.0000000000000394. — View Citation

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* Note: There are 29 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Postoperative pain evaluation	Postoperative pain will be evaluated using Numerical Rating Scale (NRS) (from 0 to 10, where 0 indicates no pain and 10 is the worst pain ever had)	day 0 (12 h after extubation)
Secondary	Opioids consumption	Quantify and compare the consumption of opioids administered to optimize analgesia ("rescue") in case of uncontrolled pain in the two groups during the observation period	within 36 hours from extubation
Secondary	Complications associated to postoperative analgesia	Detect the onset of complications related to the analgesia technique performed in the study groups	within 36 hours from extubation