Total intravenous anesthesia in kidney transplantation: A narrative review

Table 1 Risk-of-bias appraisal of included human comparative studies

Ref.	Design	Tool	Highest-risk domain(s)	Overall judgement	Comments
Aditianingsih et al[9], 2019	RCT (KT)	RoB 2	Blinding of personnel	Some concerns	Adequate randomisation; small sample size
Nieuwenhuijs-Moeke et al[10], 2017	RCT (KT)	RoB 2	Selection of reported result	Low-some concerns	Calculation-error corrigendum acknowledged
Modesti et al[2], 2006	RCT (KT)	RoB 2	Era effect; concomitant interventions	Some concerns	Dopamine infusions; HES colloids - now superseded
Babacan et al[12], 1998	RCT (KT)	RoB 2	Reporting; randomisation detail	High	Small sample size; limited methodological detail
Lee et al[3], 2013 (part-I)	Retrospective (KT)	ROBINS-I	Confounding	Serious	Non-randomised treatment allocation
Lee et al[3], 2013 (part-II)	Prospective (KT)	ROBINS-I	Confounding	Moderate	Did not confirm part-I signal
Calixto-Flores et al[13], 2020	Retrospective (KT)	ROBINS-I	Confounding; single-arm	Serious	No comparator group
Han et al[11], 2020	RCT (donors)	RoB 2	Indirectness (donors, not recipients)	Low (for donor outcomes)	Informs recovery outcomes only
Franzén et al[8], 2022	RCT (surgical patients)	RoB 2	Indirectness (surgical pts, not KT)	Low (for renal function in surgical pts)	Contemporary mechanistic evidence; indirect for KT
Liu et al[1], 2024	RCT (paediatric LRLT)	RoB 2	Indirectness (paediatric, liver, not adult KT)	Low (for liver/kidney outcomes in infants)	Mechanistic reference only; not directly extrapolable

The preclinical ovine model (Iguchi et al[7] 2019) is not amenable to Risk of Bias 2 or ROBINS-I appraisal and is omitted. HES: Hydroxyethyl starch; RCT: Randomised controlled trial; KT: Kidney transplant; RoB 2: Risk of Bias 2; LRLT: Living-related liver transplantation.

Table 2 Summary of all ten studies included in this review (six directly eligible kidney-transplant studies plus four mechanistically instructive supplementary studies)

Study	Title	Design	Population	Intervention	Key outcomes
Aditianingsih et al[9], 2019	TCI PROP vs SEVO haemodynamics in KT	Prospective RCT	46 adult KT recipients	TCI PROP vs SEVO	Similar MAP, CI, SVI; lower SVRI with PROP
Nieuwenhuijs-Moeke et al[10], 2017	PROP vs SEVO in LDKT	RCT	57 donor-recipient pairs	PROP, SEVO, PROSE	Higher urinary KIM-1, NAG with SEVO; non-significant numerical trend to higher acute rejection in PROP arm (did not reach statistical significance)
Modesti et al[2], 2006	Balanced vs TIVA for KT—older-era regimen	RCT	40 adult KT recipients	TIVA (PROP + remifentanil) vs balanced (isoflurane + fentanyl)	TIVA: Faster recovery; balanced: Marginally better early pain control (likely opioid-driven)
Babacan et al[12], 1998	Assessment of TIVA in renal transplantation—older-era regimen	RCT	18 adult KT recipients	TIVA (PROP + alfentanil) vs balanced (isoflurane + fentanyl)	Faster recovery with TIVA; better early analgesia with balanced (likely opioid-driven)
Lee et al[3], 2013	Preconditioning effects of donor anaesthetic on grafted kidney function	Retrospective + prospective	LDKT recipients (adult)	SEVO, iso, desflurane vs PROP	Desflurane: Better early estimated glomerular filtration rate (part I); no significant difference in part II
Calixto-Flores et al[13], 2020	Effect of intravenous total anaesthesia on haemodynamic changes in renal transplant	Retrospective observational (single-arm)	30 adult KT recipients	TIVA (single arm)	Stable haemodynamics; spontaneous diuresis in approximately 90%
Han et al[11], 2020	PROP vs SEVO in laparoscopic donor nephrectomy	RCT	80 healthy kidney donors	PROP vs SEVO	Higher QoR-40, better ambulation, lower PONV, shorter LOS with PROP
Franzén et al[8], 2022	Renal function during SEVO or TIVA PROP—single-centre RCT	RCT	Surgical patients (not transplant)	SEVO vs PROP-based TIVA	Contemporary mechanistic evidence on renal function under SEVO vs PROP
Liu et al[1], 2024	PROP vs desflurane in infant LRLT	RCT	76 infants with LRLT	PROP vs desflurane	Lower ALT, AST, SCr, AKI in PROP group; mechanistic relevance only
Iguchi et al[7], 2019	Renal perfusion, oxygenation, and sympathetic nerve activity during volatile or intravenous general anaesthesia in sheep	Preclinical (ovine)	Sheep	PROP-based TIVA vs volatile anaesthesia	Higher RBF and renal vascular conductance under TIVA; reduced sympathetic vasomotor drive; mechanistic background only

TIVA: Total intravenous anaesthesia; TCI: Target-controlled infusion; KT: Kidney transplant; RCT: Randomised controlled trial; MAP: Mean arterial pressure; CI: Cardiac index; SVI: Stroke volume index; SVRI: Systemic vascular resistance index; LDKT: Living-donor kidney transplant; PROP: Propofol; SEVO: Sevoflurane; PROSE: Propofol induction and sevoflurane maintenance; KIM-1: Kidney injury molecule-1; NAG: N-acetyl-β-D-glucosaminidase; PONV: Postoperative nausea and vomiting; LOS: Length of stay; LRLT: Living-related liver transplantation; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; SCr: Serum creatinine; AKI: Acute kidney injury; RBF: Renal blood flow.

Table 3 Perioperative fluid and vasoactive regimens in the eight human comparative studies

Ref.	Fluid type	Fluid strategy	Vasopressor	Mannitol/furosemide	Era effect
Aditianingsih et al[9], 2019	Balanced crystalloid	Goal-directed; SVV-guided	Norepinephrine	Mannitol 0.5 g/kg	Contemporary
Nieuwenhuijs-Moeke et al[10], 2017	Balanced crystalloid; albumin if needed	Goal-directed	Norepinephrine, ephedrine	Both, at reperfusion	Contemporary
Modesti et al[2], 2006	Crystalloid + HES colloid	Liberal; CVP-guided	Dopamine infusion	Mannitol routinely	Older era
Babacan et al[12], 1998	Crystalloid (Ringer)	Liberal	Dopamine infusion	Mannitol + furosemide	Older era
Han et al[11], 2020	Balanced crystalloid	Restrictive	Ephedrine, phenylephrine	Not reported	Contemporary
Lee et al[3], 2013	Balanced crystalloid	Goal-directed	Mixed	Mannitol; furosemide	Contemporary
Calixto-Flores et al[13], 2020	Balanced crystalloid	Goal-directed; conservative	Norepinephrine	Mannitol	Contemporary
Franzén et al[8], 2022	Balanced crystalloid	Goal-directed (per institutional protocol)	Norepinephrine	N/A (non-transplant surgery)	Contemporary

The preclinical ovine model (Iguchi et al[7] in 2019) and the paediatric living-related liver transplant trial (Liu et al[1] in 2024) are omitted because the comparison of perioperative fluid and vasopressor protocols is not directly relevant to the adult kidney transplant setting. SVV: Stroke volume variation; CVP: Central venous pressure; HES: Hydroxyethyl starch; N/A: Not available.

Table 4 Transplant-specific implications of propofol-based total intravenous anaesthesia vs volatile anaesthesia in kidney transplantation

Aspect	TIVA (propofol-based)	Volatile (sevoflurane/isoflurane/desflurane)	Clinical implication in kidney transplantation
Effect at reperfusion	Modest vasodilatation; SVR drops; manageable with norepinephrine and balanced crystalloid	Stable SVR; theoretical preconditioning via mitochondrial KATP channels	Both techniques are safe at unclamping when fluid and vasopressor support are titrated; no signal of reperfusion-related haemodynamic collapse with either
Tubular injury biomarkers (KIM-1, NAG)	Lower urinary concentrations in VAPOR-1 (n = 57 LDKT pairs)	Higher urinary concentrations in VAPOR-1	Biomarker signal favouring TIVA at the molecular level in a single small LDKT trial; not yet translated into hard clinical endpoints
Time to extubation and recovery quality	Faster (favourable context-sensitive half-time); often combined with remifentanil	Slower (pulmonary elimination, tissue accumulation); often combined with fentanyl in published comparisons	Earlier ICU step-down with TIVA, but recovery comparisons are confounded by opioid choice (see Discussion)
PONV incidence	Significantly lower (intrinsic anti-dopaminergic and 5-HT3 antiemetic effect)	Higher	Reliable early oral tacrolimus and MMF absorption—clinically important for stable trough levels in the most immunologically vulnerable post-operative phase
Acute rejection risk	Non-significant numerical trend to higher rejection in propofol arm of VAPOR-1 only; not replicated	No significant signal	No compelling evidence that anaesthetic maintenance meaningfully alters rejection risk
DGF/1-year graft survival	No demonstrated difference	No demonstrated difference	Hard clinical endpoints comparable; LDKT-dominant evidence limits generalisability to ECD/DCD recipients
Recipient-specific safety	Injection pain; hypertriglyceridaemia (lipid emulsion); rare PRIS with prolonged infusion; bacterial-contamination risk; awareness risk (no end-tidal monitoring)	Historical concern re compound A (sevoflurane in low-flow systems) now considered low-risk; end-tidal MAC monitoring straightforward	Both safe in modern practice; TIVA requires vigilance in dyslipidaemic, diabetic, or pancreatitis-prone recipients
Quality of direct KT evidence	Six small studies (< 200 recipients total); LDKT-dominant; era-heterogeneous	Same evidence pool	Conclusions for both techniques are constrained by the same small, low-risk evidence base
Practical infrastructure	TCI pump, pharmacokinetic-pharmacodynamic models, processed-EEG monitoring (e.g., BIS) for awareness mitigation	Vaporiser, end-tidal MAC monitoring	Volatile may be the practical default in resource-limited transplant programmes; TIVA preferred where TCI and processed-EEG are available

TIVA: Total intravenous anaesthesia; SVR: Systemic vascular resistance; KIM-1: Kidney injury molecule-1; NAG: N-acetyl-β-D-glucosaminidase; LDKT: Living-donor kidney transplant; ICU: Intensive care unit; PONV: Postoperative nausea and vomiting; MMF: Mycophenolate mofetil; DGF: Delayed graft function; PRIS: Propofol infusion syndrome; MAC: Minimum alveolar concentration; ECD: Extended-criteria donor; DCD: Donation-after-circulatory-death; KT: Kidney transplant; TCI: Target-controlled infusion; EEG: Electroencephalographic; BIS: Bispectral index.