Effects of general versus subarachnoid anaesthesia on circadian melatonin rhythm and postoperative delirium in elderly patients undergoing hip fracture surgery: A prospective cohort clinical trial

Abstract

Background: Circadian rhythm disturbance is common postoperatively in older patients with hip fractures, which may contribute to the development of postoperative delirium (POD). As a reliable biomarker of endogenous circadian rhythms, melatonin regulates the sleep-wake cycle and environmental adaptation, and its secretory rhythm may be modified by anaesthesia and surgery. This study compared the impact of subarachnoid anaesthesia (SA) and general anaesthesia (GA), on the peak of melatonin secretion (primary outcome), the circadian rhythm of melatonin, cortisol and sleep, and the POD incidence (secondary outcome). Methods: In this prospective cohort observational study, hip fracture surgery patients were enrolled and assigned to receive either SA or GA. Postoperative plasma melatonin and cortisol levels were dynamically measured every six hours on seven time-points, and the circadian rhythm parameters including mesor, amplitude, and acrophase were calculated. Subjective and objective sleep assessments were performed by sleep diaries and sleep trackers, respectively. The Confusion Assessment Method was used twice daily by a specific geriatrician to screen for POD occurrence. Findings: In a cohort of 138 patients who underwent hip fracture surgery, the circadian rhythm disruption of the patients in the GA group (n=69) was greater than the SA group (n=69). Compared with SA, GA provided the lower peak concentration, mesor, and amplitude of melatonin secretion on postoperative day 1 (p < 0.05). Patients in the GA group experienced higher awakenings, more sleep deprivation, and poor sleep quality on surgery day (p < 0.05). A proportion of 12 patients in the SA group (17.4%) and 24 patients in the GA group (34.8%) experienced POD (p = 0.020). Interpretation: These results suggest that SA may be superior to GA in elderly patients undergoing hip fracture surgery as SA is associated with less impairment of the melatonin rhythm and sleep patterns, and fewer POD occurrences.

Progress in Research on the Effect of Melatonin on Postoperative Cognitive Dysfunction in Older Patients

“…Melatonin is a kind of central circadian rhythm regulator, and the normal melatonin rhythm is involved in regulating the sleep-awakening cycle to some extent. All in all, there is ample evidence that melatonin production is disturbed after surgery, that perioperative sleep disorders increase the risk of POCD, and that synchronization disorders between sleep-awakening cycles and melatonin rhythms can lead to cognitive impairment ( Wright et al, 2006 ; Song et al, 2021 ; Wang X. et al, 2021 ).…”

The Effect of General Anesthesia vs. Regional Anesthesia on Postoperative Delirium—A Systematic Review and Meta-Analysis

“…Tables 1 , 2 present the basic characteristics of the included studies. There were nine retrospective ( 17 , 18 , 22 , 25 , 28 – 31 , 35 ), and 12 prospective ( 19 – 24 , 26 , 27 , 32 – 34 , 36 , 37 ) articles, including seven randomized and non-randomized controlled trials, in the prospective studies ( 20 , 23 , 24 , 32 – 34 , 37 ). Male accounted for 50% or more of all patients in 4 trials ( 17 , 22 , 23 , 25 ).…”

“…The patients in the RA group received the sole PNB in only two trials ( 17 , 29 ), and underwent PNB or neuraxial anesthesia in another two trials ( 25 , 35 ), while neuraxial anesthesia was the sole anesthesia in RA patients in the other 17 enrolled trials. The follow-up time was hospital stay after surgery in 13 trials ( 18 , 22 , 25 – 33 , 35 , 36 ), 1 year in one trial ( 23 ), 30 days in one trial ( 17 ), 1–7 days in one trial ( 20 ), 1–5 day in one trial ( 34 ), 1–4 days in one trial ( 37 ), 1–3 days in two trials ( 21 , 24 ), and 1 day in one trial ( 19 ). The methods of POD identification included antipsychotic drug use ( 17 , 18 , 22 , 30 ), Confusion Assessment Method for Intensive Care Unit (CAM-ICU) or CAM ( 19 , 21 , 36 , 37 ), DSM-IV criteria ( 24 , 27 ), NEECHAM confusion scale ( 25 ), change in mental state ( 23 ), and Pittsburgh Agitation Scale ( 26 ).…”

“…The follow-up time was hospital stay after surgery in 13 trials ( 18 , 22 , 25 – 33 , 35 , 36 ), 1 year in one trial ( 23 ), 30 days in one trial ( 17 ), 1–7 days in one trial ( 20 ), 1–5 day in one trial ( 34 ), 1–4 days in one trial ( 37 ), 1–3 days in two trials ( 21 , 24 ), and 1 day in one trial ( 19 ). The methods of POD identification included antipsychotic drug use ( 17 , 18 , 22 , 30 ), Confusion Assessment Method for Intensive Care Unit (CAM-ICU) or CAM ( 19 , 21 , 36 , 37 ), DSM-IV criteria ( 24 , 27 ), NEECHAM confusion scale ( 25 ), change in mental state ( 23 ), and Pittsburgh Agitation Scale ( 26 ). Seven articles did not provide a specific diagnostic method of POD ( 20 , 28 , 29 , 31 – 33 , 35 ), and a combination of CAM with DSM-IV criteria ( 34 ).…”

“…We used NOS to assess the risk of bias in observational studies (retrospective and prospective), and all 14 trials obtained seven stars or more, indicating high quality ( Supplementary Table 2 ) ( 17 – 19 , 21 , 22 , 25 – 31 , 35 , 36 ). We used the Cochrane Collaboration Risk of Bias Assessment tool to assess the risk of bias in RCTs.…”