Efficacy and safety of intraoperative controlled hypotension: a systematic review and meta-analysis of randomised trials.

BACKGROUND: Intraoperative controlled hypotension improves surgical field visibility by reducing blood loss (efficacy) but poses potential risks linked to organ hypoperfusion (safety). The use of controlled hypotension persists despite increasing evidence of associations between intraoperative inadvertent hypotension and adverse outcomes. Therefore, we tested the hypothesis that the focus and results of intraoperative controlled hypertension research differ across anaesthesia and surgery investigators because of differing priorities. METHODS: We systematically reviewed randomised trials comparing controlled hypotension with usual care with trials categorised by investigators' affiliation. RESULTS: We identified 48 eligible trials, of which 37 were conducted by anaesthesia investigators and 11 by surgery investigators. For the primary outcome, 54% of the anaesthesia-led trials focused on safety, whereas all (100%) surgery-led trials focused on efficacy (P=0.004). Compared with usual care, mean arterial pressure in controlled hypotension was 23% (95% confidence interval [CI] 17-29%) lower in anaesthesia trials and 30% (95% CI 14-37%) lower in surgery trials; estimated blood loss was 44% (95% CI 30-55%) less in anaesthesia trials and 38% (95% CI 30-49%) less in surgery trials. Overall, blood loss was reduced by 43% (95% CI 32-53%), and trial sequential analysis supported an efficacy conclusion. Mean arterial pressure and estimated blood loss reductions were associated (R2=0.41, P=0.002). All trials were underpowered for safety outcomes, and none adequately evaluated myocardial or renal injury. CONCLUSIONS: Anaesthesia researchers prioritised safety outcomes, whereas surgery researchers emphasised efficacy in controlled hypotension trials. Controlled hypotension significantly reduces blood loss. In contrast, safety outcomes were poorly studied. Given increasing observational evidence linking inadvertent hypotension to myocardial and renal injury, the safety of controlled hypotension remains to be addressed. SYSTEMATIC REVIEW PROTOCOL: PROSPERO (CRD42023450397).

Characteristics associated with effectiveness in postoperative delirium research: a systematic review of randomised controlled trials with meta-regression and meta-analysis.

BACKGROUND: Postoperative delirium remains prevalent despite extensive research through randomised trials aimed at reducing its incidence. Understanding trial characteristics associated with interventions' effectiveness facilitates data interpretation. METHODS: Trial characteristics were extracted from eligible trials identified through two systematic literature searches. Multivariable meta-regression was used to investigate trial characteristics associated with effectiveness estimated using odds ratios. Meta-analysis was used to investigate pooled effectiveness. RESULTS: We identified 201 eligible trials. Compared with China, trials from the USA/Canada (ratio of odds ratio, 1.89; 95% confidence interval, 1.45-2.45) and Europe/Australia/New Zealand (1.67; 1.29-2.18) had an 89% and 67% higher odds ratio, respectively, suggesting reduced effectiveness. The effectiveness was enhanced when the incidence of postoperative delirium increased (0.85; 0.79-0.92, per 10% increase). Trials with concerns related to deviations from intended interventions reported increased effectiveness compared with those at low risk (0.69; 0.53-0.90). Compared with usual care, certain interventions appeared to have reduced the incidence of postoperative delirium in low-risk trials with low-to-moderate certainty of evidence. However, these findings should be considered inconclusive because of challenges in grouping heterogeneous interventions, the limited number of eligible trials, the prevalence of small-scale studies, and potential publication bias. CONCLUSIONS: The effectiveness of postoperative delirium trials varied based on the region of trial origin, the incidence of delirium, and the risk of bias. The limitations caution against drawing definitive conclusions from different bodies of evidence. These findings highlight the imperative need to improve the quality of research on a global scale. SYSTEMATIC REVIEW PROTOCOL: PROSPERO (CRD42023413984).

Noradrenaline-induced changes in cerebral blood flow in health, traumatic brain injury and critical illness: a systematic review with meta-analysis.

BACKGROUND: Noradrenaline is a standard treatment for hypotension in acute care. The precise effects of noradrenaline on cerebral blood flow in health and disease remain unclear. METHODS: We systematically reviewed and synthesised data from studies examining changes in cerebral blood flow in healthy participants and patients with traumatic brain injury and critical illness. RESULTS: Twenty-eight eligible studies were included. In healthy subjects and patients without critical illness or traumatic brain injury, noradrenaline did not significantly change cerebral blood flow velocity (-1.7%, 95%CI -4.7-1.3%) despite a 24.1% (95%CI 19.4-28.7%) increase in mean arterial pressure. In patients with traumatic brain injury, noradrenaline significantly increased cerebral blood flow velocity (21.5%, 95%CI 11.0-32.0%), along with a 33.8% (95%CI 14.7-52.9%) increase in mean arterial pressure. In patients who were critically ill, noradrenaline significantly increased cerebral blood flow velocity (20.0%, 95%CI 9.7-30.3%), along with a 32.4% (95%CI 25.0-39.9%) increase in mean arterial pressure. Our analyses suggest intact cerebral autoregulation in healthy subjects and patients without critical illness or traumatic brain injury., and impaired cerebral autoregulation in patients with traumatic brain injury and who were critically ill. The extent of mean arterial pressure changes and the pre-treatment blood pressure levels may affect the magnitude of cerebral blood flow changes. Studies assessing cerebral blood flow using non-transcranial Doppler methods were inadequate and heterogeneous in enabling meaningful meta-analysis. CONCLUSIONS: Noradrenaline significantly increases cerebral blood flow in humans with impaired, not intact, cerebral autoregulation, with the extent of changes related to the severity of functional impairment, the extent of mean arterial pressure changes and pre-treatment blood pressure levels.