Open research questions in Anesthesia and Pain Management

What the literature leaves open

• Effective blinding of participants to the cryoneurolysis procedure is not feasible without a sham intervention. The risk of expectation bias, performance bias, and ascertainment bias due to the open-label design. The need to minimize confounding variables, including the exclusion of opioid-dependent patients.

  Preoperative CT-Guided Cryoneurolysis of the Genicular Nerves Before Total Knee Arthroplasty: Study Protocol for a Prospective Randomized Controlled Trial · 2026 · DOI

• Current pain management strategies after TKA have limitations, including the risk of opioid dependency. There is a need for effective and safe alternatives to opioid-based pain management. Preoperative CT-guided cryoneurolysis of the genicular nerves may address this gap.

  Preoperative CT-Guided Cryoneurolysis of the Genicular Nerves Before Total Knee Arthroplasty: Study Protocol for a Prospective Randomized Controlled Trial · 2026 · DOI

• The paper identifies the challenge of anatomical variability in the course of the suprascapular nerve. The challenge of providing selective sensory blockade with potential motor preservation is also identified. The paper notes the limited evidence for the PENG block in hip OA and the lack of RCTs on DPN blockade in OA.

  Ultrasound-guided peripheral nerve blocks for osteoarthritis pain management: a review of the genicular, suprascapular, PENG and deep peroneal nerve blocks · 2026 · DOI

• Overall certainty remains low to very low by GRADE criteria, - Evidence for the PENG block in hip OA remains limited, - No RCTs are currently available for DPN blockade in OA

  Ultrasound-guided peripheral nerve blocks for osteoarthritis pain management: a review of the genicular, suprascapular, PENG and deep peroneal nerve blocks · 2026 · DOI

• Abstract Background The effect of thoracic paravertebral block with liposomal bupivacaine on recovery after video-assisted thoracic surgery remains uncertain.

  Effect of thoracic paravertebral block with liposomal bupivacaine on quality of recovery after video-assisted thoracic surgery: a randomized controlled trial · 2026 · DOI

• Background The analgesic benefit of adding perineural hydromorphone (HYD) to ropivacaine (ROP) for proximal humerus fracture surgery remains unclear.

  Association of perineural hydromorphone added to ropivacaine with early analgesic outcomes in proximal humerus fracture surgery: a retrospective cohort study · 2026 · DOI

• Further research into patient- and procedure-specific factors is essential to reduce adverse pain-related outcomes.

  Does the quality of pain relief after major surgery influence the risk of postoperative complications? A prospective observational study · 2025 · DOI

• It remains uncertain whether poorly controlled postoperative pain influences the risk of postoperative complications.

  Does the quality of pain relief after major surgery influence the risk of postoperative complications? A prospective observational study · 2025 · DOI

• These findings underscore the critical importance of anesthesia choice, advocate for the preference of neuraxial techniques, and highlight the need for further research into long-term neonatal outcomes.

  Impact of general vs. neuraxial anesthesia on neonatal outcomes in non-elective cesarean sections · 2025 · DOI

• Previous studies have shown mixed results, often confounded by the inclusion of both elective and emergency cesarean section cases, varying statistical methods, and a focus solely on resuscitation immediate-term neonatal outcomes.

  Impact of general vs. neuraxial anesthesia on neonatal outcomes in non-elective cesarean sections · 2025 · DOI

• LIMITATIONS: The main limitation of this study is that measurements are limited to learners' reaction to learning and self-assessment outcomes.

  Simulation-based training in ultrasound-guided regional anaesthesia for emergency physicians: insights from an Italian pre/post intervention study · 2024 · DOI

• CONCLUSION: Studies on the efficacy and safety of lipids in pregnancy are scarce.

  Intravenous lipid emulsion for local anaesthetic systemic toxicity in pregnant women: a scoping review · 2024 · DOI

• However, its therapeutic application in pregnant patients has not yet been established.

  Intravenous lipid emulsion for local anaesthetic systemic toxicity in pregnant women: a scoping review · 2024 · DOI

• BACKGROUND: Epidural test dose for labor analgesia is controversial and varies widely in clinical practice.

  Using part of the initial analgesic dose as the epidural test dose did not delay the onset of labor analgesia: a randomized controlled clinical trial · 2024 · DOI

• However, evidence regarding the impact of different volumes of crystalloid solution on the phenylephrine infusion dosage for preventing this hypotension remains inconclusive.

  Effect of crystalloid solution co-loading infusion rate on the dose requirements of prophylactic phenylephrine for preventing hypotension following combined spinal-epidural anesthesia for cesarean delivery · 2024 · DOI

• However, the effects of PENG block on perioperative neurocognitive disorder (PND) after HA has not yet been assessed.

  Effects of pericapsular nerve group block on early postoperative cognitive function in older people undergoing hip arthroplasty: a randomized controlled clinical trial · 2024 · DOI

• There is a need to explore alternative methods for prehospital manipulation and reduction of acute limb injuries. The use of inhaled methoxyflurane for this purpose is not well described.

  Inhaled methoxyflurane for fracture reduction in prehospital extremity trauma: an observational review of HEMS clinical practice · 2026 · DOI

• This was a retrospective single-service HEMS analysis using clinician-completed electronic records entered after patient care, and is therefore vulnerable to documentation bias, incomplete recording, and some recall error. The cohort denominator was cases in which IMF was selected and delivered to support manipulation/reduction, rather than all traumatic limb injuries attended by the service. In addition, there was no prospective protocol mandating IMF as first-line therapy. The database does not contain sufficient searchable fields to allow reliable retrospective ascertainment of all limb injuries potentially suitable for IMF. As a result, confounding by indication (clinician case selection) is likely, and the reported associations may under- or overestimate effects if interpreted beyond this IMF-selected cohort. Associations observed in these data (including pre-medication) should not be interpreted as causal because of clinician selection and residual confounding. Clinical intent also had to be inferred from free-text documentation. Consequently, IMF’s role may have been misclassified in some cases (for example, where methoxyflurane was given as analgesia before procedural sedation rather than as a genuine attempt at IMF-facilitated reduction), which may underestimate the apparent success of the IMF-assisted pathway. Although equivocal cases were reviewed in detail by more than one investigator, reasons for unsuccessful reduction or escalation (e.g., pain-limited procedure, mechanical difficulty, or elective escalation) were not documented consistently enough to permit reliable subgroup categorisation. Timing of concomitant analgesia was also inconsistently recorded, limiting inference regarding sequencing or co-administration. Finally, several subgroup analyses (including anatomical location) contained small numbers, resulting in imprecise estimates and wide confidence intervals. These findings should therefore be interpreted cautiously and considered hypothesis-generating. Dowsing et al.

  Inhaled methoxyflurane for fracture reduction in prehospital extremity trauma: an observational review of HEMS clinical practice · 2026 · DOI

• Although the use of regional anaesthesia is increasing, high-quality evidence remains limited, with insufficient randomised controlled trial (RCT) evaluating the effectiveness of the pericapsular nerve group (PENG) block in the emergency department (ED).

  Ultrasound-guided pericapsular nerve group block versus intravenous morphine for pain management in older adults with hip fractures: a randomised controlled trial in the emergency department · 2026 · DOI

• There is a lack of information on the effectiveness of the erector spinae plane block in cats. The block has been evaluated in humans, but its use in veterinary medicine is limited. The study aims to address this gap by evaluating the block in cats undergoing elective ovariohysterectomy.

  Erector spinae plane block with bupivacaine contributes to intraoperative opioid sparing but provides limited postoperative pain control in cats undergoing elective ovariohysterectomy under continuous propofol infusion · 2026 · DOI

• The use of validated pain and sedation scales remains inherently subjective and dependent on behavioral interpretation, which may introduce variability and limit the precision of outcome measurements.

  Erector spinae plane block with bupivacaine contributes to intraoperative opioid sparing but provides limited postoperative pain control in cats undergoing elective ovariohysterectomy under continuous propofol infusion · 2026 · DOI

• The challenge of airway management in patients with AS. The difficulty of spinal anesthesia in patients with severe AS.

  Utility of real-time ultrasound-guided spinal anesthesia in severe ankylosing spondylitis - A case report - · 2026 · DOI

• The paper acknowledges the dependence of ultrasound-guided regional anesthesia on operator proficiency and the associated learning curve. It also recognizes the potential for complications, such as nerve injury and local anesthetic systemic toxicity. The paper notes the need for a structured, evidence-informed framework to ensure safe and effective adoption.

  Precision and pitfalls: evolving role of ultrasound-guided nerve blocks in Orthopedic perioperative pathway—a perspective · 2026 · DOI

• Future research should focus on enhancing precision, incorporating intelligent technology, and adopting more comprehensive approaches to improve patient outcomes. It should prioritize the development of technological integration, pharmacological advances, educational transformation, and new research methodologies. Research should also aim to address the challenges and limitations of implementing ultrasound-guided regional anesthesia in clinical practice.

  Precision and pitfalls: evolving role of ultrasound-guided nerve blocks in Orthopedic perioperative pathway—a perspective · 2026 · DOI

• There is a need for effective and safe anesthetic techniques for first-trimester surgical abortion. The current study addresses this gap by investigating the clinical efficacy of an alfentanil-remimazolam combination.

  Comparative effects of alfentanil-remimazolam versus fentanyl-remimazolam on anesthesia onset, emergence, and safety in first-trimester surgical abortion under intravenous anesthesia: a randomized controlled trial · 2026 · DOI

Most-cited papers in Anesthesia and Pain Management

• Long-term Analgesic Use After Low-Risk Surgery · Archives of Internal Medicine · 2012 · 714 citations
• Inadequate analgesia in emergency medicine · Annals of Emergency Medicine · 2004 · 412 citations
• Impact of Intravenous Lidocaine Infusion on Postoperative Analgesia and Recovery from Surgery · Drugs · 2010 · 324 citations
• Postoperative patient-controlled analgesia: Meta-analyses of initial randomized control trials · Journal of Clinical Anesthesia · 1993 · 314 citations
• Chronic post-surgical pain – update on incidence, risk factors and preventive treatment options · BJA Education · 2022 · 285 citations
• Regional anaesthesia in patients on antithrombotic drugs · European Journal of Anaesthesiology · 2022 · 277 citations
• Ultrasound guided erector spinae plane block reduces postoperative opioid consumption following breast surgery: A randomized controlled study · Journal of Clinical Anesthesia · 2018 · 264 citations
• Pain reduction in local anesthetic administration through pH buffering · Annals of Emergency Medicine · 1988 · 243 citations
• Efficacy of ultrasound imaging in obstetric epidural anesthesia · Journal of Clinical Anesthesia · 2002 · 236 citations
• Peripheral nerve blocks in the management of postoperative pain: challenges and opportunities · Journal of Clinical Anesthesia · 2016 · 232 citations

Most recent work

• A Randomized, Dose-Finding Study of Sphenopalatine Ganglion Block With Bupivacaine for Emergency Department Patients With Headache · Annals of Emergency Medicine · 2026
• Analgesic efficacy and safety of lidocaine administered by intravenous route vs erector spinae plane blocks following open heart surgery: An open-label, randomized clinical trial · Journal of Clinical Anesthesia · 2026
• Regional analgesia techniques as adjuncts to general anesthesia in pediatric cardiac surgery: an updated systematic review and meta-analysis of randomized controlled trials · Regional Anesthesia & Pain Medicine · 2026
• Pericapsular Nerve Group Block Improves Pain Control Compared With No Block in Patients Undergoing Hip Arthroscopy Surgery: A Systematic Review · Arthroscopy · 2026
• Remifentanil patient-controlled analgesia for labour analgesia: guidance from the obstetric anaesthetists’ association · European Journal of Anaesthesiology · 2026
• Norepinephrine in Major Abdominal Surgery: Comment · Anesthesiology · 2026
• Superficial intercostal plane blocks for post-sternotomy pain control rationale and design for the EPOCH CardioLink-10 randomized clinical trial · Current Opinion in Cardiology · 2026
• Maintenance of maternal blood pressure targets after spinal anaesthesia for caesarean delivery · Anaesthesia · 2026
• Mode of anaesthesia and persistent postoperative opioid use · Anaesthesia · 2026
• Open Radical Cystectomy Under Combined Spinal-Thoracic Epidural Anesthesia in High-Risk Patients: A Multicenter Retrospective Cohort Study · Société Internationale d’Urologie Journal · 2026

Related topics in Medicine