Genomdan Nöral Devrelere: Farmakogenetik, Rejyonal Bloklar ve Nöromodülasyonla Hassas Perioperatif Analjezi
Özet
Perioperatif ağrı, aynı cerrahi girişim uygulanan hastalarda dahi genetik yapı, ağrı fenotipi, organ rezervi ve rehabilitasyon hedeflerine göre önemli ölçüde değişir. Bu bölüm, standart multimodal protokollerden hastaya ve girişime özgü “hassas perioperatif analjezi” modeline geçişi ele almaktadır. Farmakogenetik eksende, CYP2D6’nın kodein ve tramadol yanıtı; CYP2C9’un ise NSAİİ/COX-2 inhibitörlerine maruziyet ve toksisite riski üzerindeki klinik etkileri incelenirken, OPRM1, COMT ve ABCB1 gibi adayların mevcut sınırlılıkları vurgulanmaktadır. Cerrahiye özgü rejyonal blokların motor koruma, solunum rezervi, erken mobilizasyon, rebound ağrı ve kalıcı cerrahi sonrası ağrı riskiyle birlikte seçilmesi gerektiği gösterilmektedir. Noninvaziv nöromodülasyon ile geçici perkütan periferik sinir stimülasyonu, seçilmiş fenotiplerde tamamlayıcı veya kurtarıcı seçenekler olarak değerlendirilirken, implante spinal kord veya dorsal kök ganglionu stimülasyon sistemleri bulunan hastaların perioperatif güvenliği de ele alınmaktadır. Bölüm; preoperatif değerlendirme, akılcı ilaç seçimi, rejyonal planlama, taburculuk eğitimi ve uzun dönem izlemi tek bakım hattında birleştiren multidisipliner bir yol haritası sunar. Temel mesaj, daha az opioid kullanırken daha iyi analjezi-fonksiyon dengesi, daha az komplikasyon ve daha düşük kalıcı ağrı yükü sağlamanın; genomik veri, anatomi, teknoloji ve ekip koordinasyonunun birlikte kullanılmasına bağlı olduğudur.
Perioperative pain varies substantially even among patients undergoing the same procedure because of differences in genetic background, pain phenotype, organ reserve, and rehabilitation goals. This chapter examines the transition from standardized multimodal protocols to patient- and procedure-specific precision perioperative analgesia. It reviews the clinical relevance of CYP2D6 to codeine and tramadol response and of CYP2C9 to exposure and toxicity risk with NSAIDs/COX-2 inhibitors, while defining the current limitations of candidates such as OPRM1, COMT, and ABCB1. Procedure-specific regional blocks are discussed in relation to motor preservation, respiratory reserve, early mobilization, rebound pain, and the risk of persistent postsurgical pain. Noninvasive neuromodulation and temporary percutaneous peripheral nerve stimulation are assessed as complementary or rescue options for selected phenotypes, while the perioperative safety of patients with implanted spinal cord or dorsal root ganglion stimulation systems is also addressed. The chapter offers a multidisciplinary pathway integrating preoperative assessment, rational drug selection, regional planning, discharge education, and long-term follow-up. Its central message is that achieving better analgesia–function balance, fewer complications, lower opioid exposure, and less persistent pain requires the coordinated use of genomic information, surgical anatomy, technology, and team-based care.
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