Efficacy and safety of procedural sedation-analgesia during laser photocoagulation for retinopathy of prematurity: a systematic review

Clinical Snapshot

Key Findings

• P Value: Not reported at the systematic review level; individual trial-level statistics not extractable from the abstract

• Effect Size: No pooled effect size calculable due to clinical and methodological heterogeneity across the four included RCTs; narrative synthesis only

• Primary Outcome: Three of four RCTs evaluating pain-related outcomes (PIPP-R score and intra-procedural crying duration) found that non-GA sedation-analgesia regimens may provide inadequate procedural analgesia, with most infants continuing to experience moderate-to-severe procedural pain

• Nnt Or Sensitivity: Not calculable from available data; apnoea incidence with high-dose fentanyl reported at 30% — a clinically significant harm signal. Ketamine-propofol effect on post-procedure ventilation requirement described as 'very uncertain' compared with GA

• Confidence Interval: Not reported; GRADE certainty rated as low to very low across outcomes

Clinical Application

The review highlights a critical evidence gap rather than providing actionable guidance. Where GA is available and safe, it remains the standard of care. In resource-limited or regional settings, clinicians must balance the risks of inadequate analgesia against the documented 30% apnoea risk with high-dose fentanyl. No regimen can currently be recommended with confidence as a GA alternative based on this evidence. In Australia, laser photocoagulation for ROP is predominantly performed under general anaesthesia in tertiary NICUs, consistent with ANZNN and RACGP/RACP neonatal guidelines. The TGA-approved agents discussed (fentanyl, ketamine, propofol) are available in Australian settings. The PBS does not specifically list oral sucrose or dextrose for procedural analgesia, though these are used as standard non-pharmacological adjuncts in Australian NICUs per NHMRC pain management guidance. This review's findings are most relevant to Australian regional and remote NICUs where anaesthetic support may be limited, and to advocacy for adequate resourcing of GA services for ROP laser procedures. The 30% apnoea rate with high-dose fentanyl is a critical safety consideration for any Australian centre considering fentanyl-based protocols without full resuscitation support. Preterm neonates (particularly those born at very low gestational age) requiring laser photocoagulation for type 1 or threshold ROP, particularly in settings where general anaesthesia is unavailable or logistically challenging

Abstract

UNLABELLED: Laser photocoagulation for retinopathy of prematurity (ROP) in preterm infants causes significant procedural pain. Although general anaesthesia (GA) is the standard of care, many settings frequently rely on inadequate sedation-analgesia or topical anaesthesia alone, exposing neonates to considerable pain and clinical instability. This systematic review aimed to evaluate the efficacy and safety of procedural sedation-analgesia during laser photocoagulation for ROP. We searched MEDLINE, Embase, and Cochrane CENTRAL for trials investigating sedation-analgesic agents during laser photocoagulation. Primary outcome was analgesic efficacy (pain score reduction, rescue analgesics required). Additional outcomes included adverse effects (e.g., apnea, oxygen requirement). Two reviewers extracted relevant information and assessed risk-of-bias using ROB2 and evidence certainty using GRADE methodology. Of 540 articles screened, four relevant RCTs were identified (n = 265). These RCTs compared varying combinations of agents (oral dextrose vs. no dextrose, fentanyl vs. oral sucrose, fentanyl vs. ketamine, ketamine-propofol vs. GA). Three RCTs evaluating pain-related outcomes (PIPP-R score and intra-procedural crying duration) suggested that the investigated non-general anaesthetic regimens may provide inadequate procedural analgesia (low to very low-certainty evidence). The evidence is very uncertain about the effect of ketamine-propofol on post-procedure ventilation requirement compared with general anaesthesia. Apnea was the commonest adverse effect (three studies), especially with high-dose fentanyl (30%). Three studies had a low risk-of-bias, while one had some concerns (randomisation, outcome measurement). CONCLUSION: Overall, the included studies were small RCTs evaluating varying combinations of interventions, precluding concrete conclusions about the superiority of any analgesic regimen during laser photocoagulation. Further high-quality studies are needed to identify safe and effective analgesia for settings where GA is unavailable. REVIEW REGISTRATION: Prospectively registered on PROSPERO (CRD420251070146). WHAT IS KNOWN: • Laser photocoagulation procedure for retinopathy of prematurity is immensely painful. • Despite general anaesthesia being the standard, most neonates undergo the procedure under inadequate analgesia, particularly in high-burden settings. Optimal analgesic regimen for the laser procedure, in settings where general anaesthesia is unavailable, is unknown. WHAT IS NEW: • This systematic review of trials investigating analgesic agents for laser procedure for ROP found four RCTs with significant heterogeneity in intervention agents. • Low- to very low-certainty evidence suggests that none of the evaluated sedo-analgesic regimens consistently achieved optimal analgesia, and most infants continued to experience moderate-to-severe procedural pain.

References

1. 1.Prakash, S., Thomas, D., Madathil, S., & Kainth, D. (2026). Efficacy and safety of procedural sedation-analgesia during laser photocoagulation for retinopathy of prematurity: a systematic review. European Journal of Pediatrics. https://doi.org/10.1371/journal.pmed.0050129