Preoperative butyrylcholinesterase activity and risk of postoperative delirium: A meta-analysis

Table 1 Characteristics of the included studies

Ref.	Country	Design	Patients’ characteristics	No. of patients included	Mean age (years)	Men (%)	Anesthesia	Timing of ChE measuring	Method for measuring ChE	Follow-up duration	Method(s) for diagnosis of POD	No. of patients with POD	Outcome reported	Variables matched or adjusted
Zajonz et al[16], 2023	Germany	PC	Adults undergoing elective isolated on-pump CABG	93	65.6	87.1	General anesthesia	Preoperative	Bedside photometric testing	7 days after surgery	CAM-ICU and ICDSC	20	Difference of AChE and BuChE activity between patients with and without POD	Age, sex, EuroSCORE, HbA1c, diabetes, CPB duration, intraoperative variables
Gruendel et al[17], 2024	Germany	PC	Adults > 70 years undergoing scheduled (hip/knee) or emergency (hip/arm) orthopedic surgery	151	81.4	29.8	General or spinal anesthesia	Preoperative (within 24 hours before surgery)	Bedside photometric testing	7 days after surgery	CAM	38	Difference of AChE and BuChE activity between patients with and without POD	Age, sex, ASA, CCI, MMSE, Frailty Score, GDS, MNA, CDT
Schlake et al[18], 2024	Germany	PC	Adults undergoing elective cardiothoracic surgery or TAVI	237	74	63.4	General anesthesia	Preoperative	Photometric method	3 days after surgery	CAM or CAM-ICU	94	Difference of BuChE activity between patients with and without POD, and OR of BuChE activity for POD	Age, MoCA score at baseline type 2 diabetes, coronary heart disease, surgery type, red cell concentrate transfusion
Cerejeira et al[25], 2011	Portugal	PC	Older patients (≥ 60 years) undergoing elective THA	101	73	49.5	NR	At admission	Colorimetric assay	3 days after surgery	CAM criteria confirmed by DSM-IV-TR	37	Difference of AChE and BuChE activity between patients with and without POD	Age, sex, alcohol use, comorbidities, anti-cholinergic drug burden, and laboratory markers
Müller et al[26], 2019	Germany	PC	Adults undergoing elective inpatient surgery across various surgical disciplines	650	61.5	52.8	General anesthesia	Pre-op (≥ 1 day and just before induction)	Bedside photometric testing	3 days after surgery	Nu-DESC	179	Difference of AChE and BuChE activity between patients with and without POD, and OR of AChE and BuChE activity for POD	Age, sex, ASA PS, NYHA class, comorbidities, severity/duration of surgery and anesthesia, RASS scores, anti-cholinergic burden, transfusions, fluids, hemoglobin level
Adam et al[27], 2020	Germany	PC	Adults undergoing elective cardiac surgery	114	70.4	72.8	General anesthesia	Preoperative morning	Bedside photometric testing	2 days after surgery	CAM-ICU	31	Difference of AChE and BuChE activity between patients with and without POD, and OR of AChE and BuChE activity for POD	Age, sex, EuroSCORE, and anti-cholinergic use
Lin et al[28], 2020	China	PC	Older patients (≥ 65 years) undergoing elective TKA or THA	447	72.3	47.2	Combined spinal-epidural anesthesia	Preoperative (before anesthesia during spinal puncture)	Spectrophotometry	7 days after surgery	CAM criteria with severity rated by MDAS	51	Difference of AChE and BuChE activity between patients with and without POD	Age, sex, education, height, weight, BMI, ASA class
Chen et al[29], 2021	China	RC	Older patients (≥ 60 years) undergoing elective TKA or THA	116	85.6	22.4	General anesthesia	Preoperative	NR	3 days after surgery	CAM criteria	58	OR of BuChE activity for POD	Age, sex, smoking, alcohol drinking, comorbidities, history of mental illness/psychotropic drugs, transfusion, anesthesia, surgical approach, surgical grade, EF, LDH, Cystatin C, arrhythmia, and operation duration
Guenther et al[30], 2021	Germany	PC	Older patients (≥ 60 years) undergoing elective cardiac surgery	51	72	69.8	General anesthesia	Preoperative	Clinical chemistry analyzer	ICU stay	CAM-ICU	20	Difference of BuChE activity between patients with and without POD, and OR of BuChE activity for POD	Age, sex, EuroSCORE, Hb, platelets, and CPB time
Saha et al[31], 2021	Germany	PC	Adults undergoing elective cardiac surgery	107	66.9	80.4	General anesthesia	Preoperative	Clinical chemistry analyzer	5 days after surgery	CAM-ICU and ICDSC	34	Difference of BuChE activity between patients with and without POD	Age, sex, baseline MMSE, anti-cholinergic burden, and surgical characteristics
Takano et al[32], 2021	Japan	RC	Older patients (≥ 65 years) undergoing emergency major GI surgery	60	80.1	43.3	General anesthesia	Preoperative (within 48 hours before surgery)	Routine biochemical tests	30 days after surgery	Medical chart evidenced	7	OR of BuChE activity for POD	None
Bosancic et al[33], 2022	Germany	PC	Older patients (≥ 65 years) undergoing elective abdominal surgery	127	72.4	41	General, regional, or combined	Preoperative (morning of surgery)	Bedside photometric testing	7 days after surgery	CAM or CAM-ICU	52	Difference of AChE and BuChE activity between patients with and without POD, and OR of AChE and BuChE activity for POD	Age, sex, duration of surgery, and CCI
Chen et al[34], 2023	China	RC	Older patients (≥ 60 years) undergoing elective THA	476	78.4	33.8	General anesthesia	Preoperative	Routine biochemical tests	3 days after surgery	CAM	86	OR of BuChE activity for POD	None

ChE: Cholinesterase; POD: Postoperative delirium; PC: Prospective cohort; RC: Retrospective cohort; CABG: Coronary artery bypass grafting; CAM-ICU: Confusion Assessment Method for the Intensive Care Unit; ICDSC: Intensive Care Delirium Screening Checklist; AChE: Acetylcholinesterase; BuChE: Butyrylcholinesterase; EuroSCORE: European System for Cardiac Operative Risk Evaluation; CPB: Cardiopulmonary bypass; CAM: Confusion Assessment Method; ASA: American Society of Anesthesiologists Physical Status Classification; CCI: Charlson Comorbidity Index; MMSE: Mini-Mental State Examination; GDS: Geriatric Depression Scale; MNA: Mini Nutritional Assessment; CDT: Clock Drawing Test; TAVI: Transcatheter aortic valve implantation; OR: Odds ratio; MoCA: Montreal Cognitive Assessment; THA: Total hip arthroplast; NR: Not reported; DSM-IV-TR: Diagnostic and Statistical Manual-Fourth Edition, Text Revision; Nu-DESC: Nursing Delirium Screening Scale; PS:; NYHA: New York Heart Association Classification; RASS: Richmond Agitation-Sedation Scale; TKA: Total knee arthroplasty; MDAS: Memorial Delirium Assessment Scale; BMI: Body mass index; EF: Ejection fraction; LDH: Lactate dehydrogenase; Hb: Hemoglobin; GI: Glycaemic index.

Table 2 Study quality evaluation via the Newcastle-Ottawa Scale

Ref.	Representativeness of the exposed cohort	Selection of the non-exposed cohort	Ascertainment of exposure	Outcome not present at baseline	Control for age and sex	Control for other confounding factors	Assessment of outcome	Enough long follow-up duration	Adequacy of follow-up of cohorts	Total1
Zajonz et al[16], 2023	1	1	1	1	1	1	1	1	1	9
Gruendel et al[17], 2024	1	1	1	1	1	1	1	0	1	8
Schlake et al[18], 2024	1	1	1	1	1	1	1	0	1	8
Cerejeira et al[25], 2011	1	1	1	1	1	1	1	0	1	8
Müller et al[26], 2019	1	1	1	1	1	1	1	0	1	8
Adam et al[27], 2020	1	1	1	1	1	1	1	0	1	8
Lin et al[28], 2020	1	1	1	1	1	1	1	1	1	9
Chen et al[29], 2021	0	1	1	1	1	1	1	0	1	7
Guenther et al[30], 2021	1	1	1	1	1	1	1	0	1	8
Saha et al[31], 2021	1	1	1	1	1	1	1	1	1	9
Takano et al[32], 2021	1	1	1	1	0	0	1	1	1	7
Bosancic et al[33], 2022	1	1	1	1	1	1	1	1	1	9
Chen et al[34], 2023	1	1	1	1	0	0	1	1	1	7

¹Each item scored as 1 if the criterion was fulfilled and 0 if not; total score represents the sum across domains (maximum = 9).