Dear Editor, Intrathecal administration of local anaesthetics (LAs) remains a keystone of central neuraxial block, particularly for abdominal and lower limb surgeries. Given the limited duration of single-shot LAs, the addition of adjuvants plays a critical role in improving block quality by accelerating onset, prolonging analgesia, reducing LA requirements, and even minimising adverse effects such as hypotension.1 Numerous pharmacological agents have been used as adjuvants over the past decades; however, there appears to be a regulatory gap between widespread clinical use and formal regulatory approval. Currently, morphine, ziconotide, and baclofen are the only agents approved by the United States Food and Drug Administration for intrathecal use for chronic pain and spasticity, and morphine is the only on-label adjuvant for routine single-shot spinal anaesthesia (SA).2 Other adjuvants Table 1, such as clonidine, dexmedetomidine, buprenorphine, nalbuphine, magnesium sulphate, neostigmine, midazolam, and dexamethasone, are widely used to enhance intrathecal block characteristics, though their use remains off-label.3Table 1: Various intrathecal adjuvants used in spinal anaesthesiaHigh-quality evidence supports the efficacy and short-term safety of several agents. Clonidine prolongs sensory blockade by 1–3 h without major haemodynamic effects at doses ≤15–30 μg and potential influence on haemodynamics at higher doses. Dexmedetomidine (3–5 μg) extends post-operative analgesia by up to 4 h, reduces opioid need, and decreases nausea. Dexamethasone (4–8 mg) shows promise as an adjuvant with evidence of short-term safety, though caution is advised due to rare reports of potential neuroinflammation and ongoing need for long-term data.4 Midazolam and ketamine also enhance analgesia duration without significant respiratory depression. While high-quality evidence supports short-term efficacy and safety for several agents, animal studies and rare reports highlight potential neurotoxicity risks. Preservative-free formulations are essential to minimise such risks. These findings reflect a shift towards multimodal, evidence-based neuraxial techniques, including applications in thoracic segmental SA.5 This evidence–regulatory mismatch is a global problem and carries disproportionate risk. Though off-label intrathecal adjuvant use is well recognised in anaesthesia, risks such as arachnoiditis, delayed neurotoxicity, and under-reported complications in resource-limited settings underscore the need for vigilance.6 This evidence–regulatory gap raises ethical and safety concerns, especially in low- and middle-income countries, where off-label practices are common due to limited access to approved formulations. The risk is compounded by variable drug quality, lack of preservative-free formulations, limited reporting of adverse events, and inconsistent adherence to standardised protocols. Given that SA is the preferred anaesthesia technique in a significant proportion of surgeries, adopting adjuvants without standardised, certified guidelines (despite available evidence) may worsen outcome disparities. The anaesthesia societies and associations could consider initiating multi-centre trials and formulating national guidelines to ensure the safe, standardised use, including recommended safe dose ranges for intrathecal adjuvants. This would allow anaesthesiologists to individualise dosing, according to patient and surgical characteristics. Despite regulatory constraints, cumulative evidence supports the cautious, evidence-informed use of intrathecal adjuvants to optimise outcomes. Clinicians should balance innovation with patient safety, guided by research, restricting themselves to preservative-free drugs, obtaining explicit informed consent, and pharmacovigilance. The time has come to convert widespread off-label practice into regulated, evidence-informed care—for the safety of millions of patients who receive SA every year. Disclosure of use of artificial intelligence (AI)-assistive or generative tools Basic grammar and spelling checks were performed using Quill Bot. Author contributions IAK was involved in concept, review of literature, initial draft preparation, editing, review and approval. HMK was involved in revision, adding intellectual content, editing, review and approval. All the authors have participated in the review, drafting and final approval of the manuscript. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
Khan et al. (Sun,) studied this question.