Experience with an opioid peptide (tyrosyl-D-arginyl-phenylalanyl-glycine amide) in oncology: a comparative randomized clinical study

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Abstract

Background: The application of tyrosyl-D-arginyl-phenylalanyl-glycine amide, a highly specific μ1-opioid receptor agonist, represents a promising approach for managing acute postoperative pain.

Aim: To evaluate the efficacy and safety of tyrosyl-D-arginyl-phenylalanyl-glycine amide in oncology patients, depending on the type of anesthesia used for various surgical interventions.

Materials and methods: A comparative randomized clinical study included 80 patients aged 29–86 years [median age (Me) 66 years, interquartile range (Q1; Q3) 59–71 years], of whom 46 (57.5%) were men and 34 (42.5%) were women, classified as American Society of Anesthesiologists (ASA) physical status I–III. These patients underwent planned surgical treatment for oncological diseases. Patients received either multimodal combined general anesthesia with mechanical ventilation in the control group (Group K, n=40) or combined anesthesia (general+epidural/intercostal block for thoracic surgeries) in the comparison group (Group C, n=40). All patients were administered a standardized postoperative systemic analgesia protocol based on tyrosyl-D-arginyl-phenylalanyl-glycine amide at a dose of 4 mg 3 times per day. The first dose was administered when pain intensity exceeded 3 points at rest and 4 points during movement on the Numeric Rating Scale (NRS). Pain intensity was assessed at rest and during movement at predetermined time points: 15, 30, 45, 60, 120, and 240 minutes after the first dose.

Results: Baseline pain intensity at rest (NRS) was higher in Group K compared to Group C [Me=6, (Q1; Q3)=(5; 5) and (5; 6), respectively; p=0.038]. While initial pain intensity during movement was similar between groups (Me=7 points), the interquartile range was greater in Group K [(Q1; Q3) = (6; 8)] compared to Group C [(6; 7); p=0.045]. Lower pain scores were observed in Group C at 45 and 60 minutes at rest (p=0.005 and p=0.008, respectively) and at 30 minutes during movement (p=0.036).

Conclusion: The combination of tyrosyl-D-arginyl-phenylalanyl-glycine amide with regional perioperative blocks is an optimal method for managing acute pain in the early postoperative period for patients undergoing complex and traumatic oncological surgeries.

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About the authors

Tatyana D. Lukonina

National Medical Research Center of Radiology

Author for correspondence.
Email: tatiyana.kretowa@yandex.ru
ORCID iD: 0009-0002-1203-2395
SPIN-code: 7937-3507

MD, anesthesiologist-resuscitator, Herzen Moscow Research Institute of Oncology

Russian Federation, 3 2nd Botkinskii roadway, 125284 Moscow

Victoria E. Khoronenko

National Medical Research Center of Radiology; Peoples’ Friendship University of Russia

Email: khoronenko_mnioi@mail.ru
ORCID iD: 0000-0001-8845-9913
SPIN-code: 1971-6546

MD, Dr. Sci. (Medicine), Professor, Herzen Moscow Research Institute of Oncology

Russian Federation, 3 2nd Botkinskii roadway, 125284 Moscow; Moscow

Guzal R. Abuzarova

National Medical Research Center of Radiology; Russian Medical Academy of Continuous Professional Education

Email: abuzarova_mnioi@bk.ru
ORCID iD: 0000-0002-6146-2706
SPIN-code: 9876-4680

MD, Dr. Sci. (Medicine), Professor, Herzen Moscow Research Institute of Oncology

Russian Federation, 3 2nd Botkinskii roadway, 125284 Moscow; Moscow

Anna S. Malanova

National Medical Research Center of Radiology

Email: malanova_anna@mail.ru
ORCID iD: 0000-0003-4222-6959
SPIN-code: 4360-6385

MD, Cand. Sci. (Medicine), Herzen Moscow Research Institute of Oncology

Russian Federation, 3 2nd Botkinskii roadway, 125284 Moscow

Anastasiia A. Ageeva

National Medical Research Center of Radiology

Email: stya.mars@gmail.com
ORCID iD: 0000-0002-8669-6648
SPIN-code: 8032-1449

MD, anesthesiologist-resuscitator, Herzen Moscow Research Institute of Oncology

Russian Federation, 3 2nd Botkinskii roadway, 125284 Moscow

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Supplementary files

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2. Appendix 1
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3. Fig. 1. Graphical scheme of the study. n — number of patients, ОАК — complete blood count, БХ анализ — biochemical analysis, ОАМ — urinalysis, ЭКГ — electrocardiogram, Rg-ОГК — chest x-ray, ASA — american society of anesthesiologists, classification of the patient’s physical status according to the american society, ECOG — eastern cooperative oncology group performance score, a scale for assessing the overall condition of oncology patients, MoCA — montreal cognitive assessment, a test used for screening cognitive impairments, п/к — subcutaneous administration, ЖВП — vital signs, АД — blood pressure, ЧСС — heart rate, НЯ — adverse events, К — control group, type of anesthetic management — combined general anesthesia, basis for postoperative analgesia — selective opioid agonist, additional use of other non-opioid analgesics and their combinations was permitted, C — comparison group, patients received combined anesthesia, regional blocks were used for analgesia during surgery and in the postoperative period, methods of systemic analgesia were similar to those in group.

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4. Fig. 2. Analysis by group according to the “ECOG performance status”. Group К — control group; group С — comparison group, 0 — patient is fully active, able to perform all activities as before the illness, 1 — patient is unable to perform heavy work but can engage in light or sedentary tasks (e.g., light household or clerical work,), 2 — patient is receiving outpatient treatment, capable of self-care, but cannot perform work, spending more than 50% of awake time actively in an upright position, 3 — patient can only perform limited self-care and spends more than 50% of awake time in a chair or bed.

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5. Fig. 3. Dynamics of the NRS pain intensity index (points) when measured at rest in the cis groups before administration and at control points. Me — median value of the pain intensity indicator, the control points are indicated on the abscissa axis: 0 — before and after 15, 30, 45, 60, 120, 240 minutes after administration of a selective opioid agonist (tyrosyl-d-arginyl-phenylalanyl-glycine amide).

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6. Fig. 4. Dynamics of the pain intensity index according to nrs (scores) during movement in groups k and c before administration and at control points. Me — median value of the pain intensity index; control points are indicated on the x-axis: 0 — before and 15, 30, 45, 60, 120, and 240 minutes after the administration of selective opioid agonist (tyrosyl-d-arginyl-phenylalanine-glycine amide).

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