Importance of sequential methods in meta-analysis: implications for postoperative mortality, delirium, and stroke management.

Trial sequential analysis is an adaptation of frequentist sequential methods that can be used to improve inferences from meta-analysis. Trial sequential analysis can help preserve type I and type II error rates at desired levels for analyses conducted before the required information size. Through three case studies recently published in the British Journal of Anaesthesia, we show how trial sequential analysis can inform the interpretation of meta-analyses. Limitations of trial sequential analysis, which also include those of the meta-analysis to which it is applied, must be carefully considered alongside its benefits.

Impact of female sex on anaesthetic awareness, depth, and emergence: a systematic review and meta-analysis.

BACKGROUND: Suggested anaesthetic dose ranges do not differ by sex, likely because of limited studies comparing sexes. Our objective was to systematically synthesise studies with outcomes of unintended anaesthesia awareness under anaesthesia, intraoperative connected consciousness, time to emergence from anaesthesia, and dosing to achieve adequate depth of anaesthesia, and to compare between females and males. METHODS: Studies were identified from MEDLINE, Embase, and the Cochrane library databases until August 2, 2022. Controlled clinical trials (randomised/non-randomised) and prospective cohort studies that reported outcomes by sex were included. Results were synthesised by random effects meta-analysis where possible, or narrative form. RESULTS: Of the 19 749 studies identified, 64 (98 243 participants; 53 143 females and 45 100 males) were eligible for inclusion, and 44 citations contributed to meta-analysis. Females had a higher incidence of awareness with postoperative recall (33 studies, odds ratio 1.38, 95% confidence interval [CI] 1.09-1.75) and connected consciousness during anaesthesia (three studies, OR 2.09, 95% CI 1.04-4.23) than males. Time to emergence was faster in females, including time to eye-opening (10 studies, mean difference -2.28 min, 95% CI -3.58 to -0.98), and time to response to command (six studies, mean difference -2.84 min, 95% CI -4.07 to -1.62). Data on depth of anaesthesia were heterogenous, limiting synthesis to a qualitative review which did not identify sex differences. CONCLUSIONS: Female sex was associated with a greater incidence of awareness under general anaesthesia, and faster emergence from anaesthesia. These data suggest reappraisal of anaesthetic care, including whether similar drug dosing for females and males represents best care. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022336087.

Depth of anaesthesia and mortality after cardiac or noncardiac surgery: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Recent randomised controlled trials have failed to show a benefit in mortality by using processed electroencephalography (pEEG) to guide lighter anaesthesia. We performed a meta-analysis of mortality data from randomised trials of pEEG monitoring to assess the evidence of any protective effect of pEEG-guided light anaesthesia compared with deep anaesthesia in adults aged ≥18 yr. METHODS: Our study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. In February 2022, we searched three databases (Cochrane CENTRAL, OVID Medline, EMBASE) for RCTs of pEEG monitoring that provided mortality data at 30 days, 90 days, and/or 1 yr or longer. RESULTS: We included 16 articles from 12 RCTs with 48 827 total participants. We observed no statistically significant mortality reduction with light anaesthesia compared with deep anaesthesia in patients aged ≥18 yr when all studies were pooled (odds ratio [OR]=0.99; 95% confidence interval (CI), 0.92-1.08). This result did not change significantly when analysing mortality at 30 days, 90 days, 1 yr or longer. We observed no mortality benefit for pEEG monitoring compared with usual care (OR=1.02; 95% CI, 0.89-1.18), targeting higher pEEG index values compared with lower values (OR=0.89; 95% CI, 0.60-1.32), or low pEEG index value alerts compared with no alerts (OR=1.02; 95% CI, 0.41-2.52). CONCLUSIONS: pEEG-guided lighter anaesthesia does not appear to reduce the risk of postoperative mortality. The absence of a plausible rationale for why deeper anaesthesia should increase mortality has hampered appropriate design of definitive clinical trials. CLINICAL TRIAL REGISTRATION: CRD42022285195 (PROSPERO).

Direct hospital costs of total laparoscopic hysterectomy compared with fast-track open hysterectomy at a tertiary hospital: a retrospective case-controlled study.

AIMS: To assess the direct intraoperative and postoperative costs in women undergoing total laparoscopic hysterectomy and fast-track open hysterectomy. METHODS: A retrospective review of the direct hospital-related costs in a matched cohort of women undergoing total laparoscopic hysterectomy (TLH) and fast-track open hysterectomy (FTOH) at a tertiary hospital. All costs were calculated, including the cost of advanced high-energy laparoscopic devices. The effect of the learning curve on cost in laparoscopic hysterectomy was also assessed, as was the hospital case-weighted cost, which was compared with the actual cost. RESULTS: Fifty women were included in each arm of the study. TLH had a higher intraoperative cost, but a lower postoperative cost than FTOH (AUD$3877 vs AUD$2776 P < 0.001, AUD$3965 vs AUD$6233 P < 0.001). The total cost of TLH was not different from FTOH (AUD$7842 vs AUD$9009 P = 0.068) and after a learning curve; TLH cost less than FTOH (AUD$6797 vs AUD$8647, P < 0.001). The use of high-energy devices did not impact on the cost benefit of TLH, and hospital case-weight-based funding correlated poorly with actual cost. CONCLUSION: Despite the use of fast-track recovery protocols, the cost of TLH is no different to FTOH and after a learning curve is cheaper than open hysterectomy. Judicious use of advanced energy devices does not impact on the cost, and hospital case-weight-based funding model in our hospital is inaccurate when compared to directly calculated hospital costs.

Dilemmas in biomedical research publication: are we losing the plot?

PURPOSE OF REVIEW: Some recent and very controversial developments in the sphere of scientific publication, with significant implications for biomedical research, are posing a significant threat to traditional publication models. Many of these developments appear to be the result of a vicious circle that has developed from publication pressure on researchers, corporate financial exploitation of those pressures, and an apparent perception that individual and institutional reputations are to be promoted at all cost. RECENT FINDINGS: The detrimental effects of these developments have led to a groundswell of academic discontent and a 'researcher uprising' that may result in precipitous changes. SUMMARY: In many different respects, biomedical research publication is now in an unprecedented state of flux. Traditional models are being strongly challenged, probably with good reason, and alternative models of both funding and delivery need to be settled upon with some urgency. While individuals, institutions and corporate bodies who resist the current evolution may find themselves in line for extinction, at the same time it is important for the entire 'industry' to revert to some more traditional values and not allow self-interest to prevail.

Effects of sevoflurane versus propofol on cerebral autoregulation during anaesthesia for robot-assisted laparoscopic prostatectomy.

Robot-assisted laparoscopic prostatectomy requires a pneumoperitoneum combined with steep Trendelenburg positioning, and these conditions can be associated with impairment of cerebral autoregulation. The objective of this study was to determine if choice of anaesthetic agent affects the preservation of cerebral autoregulation during robot-assisted laparoscopic prostatectomy. We randomly assigned 30 patients to maintenance of general anaesthesia with either propofol or sevoflurane. Cerebral autoregulation was tested by administration of intravenous phenylephrine to increase mean arterial pressure from approximately 80 mmHg to 100 mmHg while assessing cerebral blood flow using transcranial Doppler ultrasonography. Autoregulation was first tested in the supine position and then approximately once every hour after Trendelenburg positioning. The main outcome measure was the result of the final autoregulation test prior to completion of surgery. At that time, we found cerebral autoregulation to be significantly impaired in six of the 15 patients receiving sevoflurane and none of the 15 patients receiving propofol (P = 0.02). However, it should be noted that some patients in the propofol group had impaired autoregulation on earlier tests. In conclusion, we found that autoregulation during robot-assisted laparoscopic prostatectomy is less likely to be impaired with propofol compared to sevoflurane anaesthesia, particularly towards the end of the surgery.

The role of transversus abdominis plane blocks in women undergoing total laparoscopic hysterectomy: a retrospective review.

INTRODUCTION: The transversus abdominis plane (TAP) local anaesthetic block is beneficial in patients undergoing open pelvic surgery; however, there are no data on its use in women undergoing laparoscopic gynaecologic surgery. METHODS: Successive women undergoing TLH were included in this review. All women had local anaesthetic infiltration at the site of port placement and, in addition, received multimodal post-operative analgesia. RESULTS: Sixty-one successive cases were included in the study: 20 had a TAP block and 41 were managed without any blocks. The groups were comparable with respect to age, body mass index, Eastern Co-operative Group performance status, type of operation, cancer status, surgical and anaesthetic time. Women with a TAP block had a significantly shorter length of stay (1.45 vs 2.20 days, P=0.014), lower total peri-operative and post-operative opioid use (12 vs 19 mg in morphine equivalents, P=0.014; 11 vs 21 mg, P=0.05) when compared with those without a TAP block. Multivariate analysis identified patient age and a TAP block with a shorter length of stay (P<0.001 and P=0.015, respectively). Total opioid use was only significantly correlated with a TAP block (P=0.005). There were no complications related to a TAP block. CONCLUSION: A TAP block in women undergoing TLH results in significantly shorter length of stay and lower opioid use. The retrospective nature of this trial and the absence of data on pain scores and nausea and vomiting are best addressed by a large prospective study.

Perioperative outcomes after total laparoscopic hysterectomy compared with fast-track open hysterectomy - a retrospective case-control study.

AIMS: To examine perioperative outcomes after total laparoscopic hysterectomy compared with fast-track open hysterectomy using a retrospective case-control study. METHODS: Consecutive cases of total laparoscopic hysterectomy (TLH) carried out by a single surgeon were matched with cases of fast-track open hysterectomy (FTOH) carried out by a second surgeon. Women were matched for age, body mass index, European Cooperative Oncology Group performance status, benign or malignant disease and extent of surgery. RESULTS: Fifty women were included in each group; women undergoing TLH had a shorter hospital inpatient length of stay (LOS) (1.82 vs 2.62 days, P = 0.02), but longer total theatre time (TT) and surgical time (ST) (226 vs 182 min, P = 0.05; 172 vs 137 min, P = 0.04). LOS, TT and OT were shorter in the second 25 women undergoing TLH than the first 25 cases (1.8 days vs 2.6 days (P = 0.02); 137 min vs 173 min (P = 0.04); 200 min vs 226 min (P = 0.05). A comparison of the second 25 women undergoing TLH with the matched cohort undergoing FTOH revealed a shorter LOS, but no difference in TT or ST (1.8 days vs 3.4 days (P < 0.001); 175 min vs 200 min (P = 0.33); 137 min vs 144 min (P = 0.48)). There were no readmissions in the TLH group and two in the FTOH group, one for a wound infection and another for a small bowel obstruction. CONCLUSION: A TLH results in significantly shorter inpatient stay than FTOH and after an initial learning curve does not result in prolonged theatre or surgical times.

Adding low concentrations of clonidine to ropivacaine for transversus abdominis plane blocks does not reduce plasma ropivacaine levels, suggesting a lack of vasoconstrictor effect.

Clonidine has been used successfully to prolong the duration of action of local anaesthetics in peripheral nerve blocks, but its mechanism of action in this setting remains unclear. Some studies suggest that clonidine exerts a vasoconstrictor effect, limiting the washout of local anaesthetic from its site of deposition. We investigated this potential vasoconstrictor effect, using plasma ropivacaine concentrations as a surrogate measure of vasoconstriction, in patients who received transversus abdominis plane (TAP) blocks with and without clonidine. Eighty women undergoing laparoscopic gynaecological surgery were randomly assigned to receive one of four TAP block solutions: 0.2% ropivacaine (control), ropivacaine with clonidine 2 µg/kg (clonidine), ropivacaine with 1:400,000 adrenaline (adrenaline) or ropivacaine and a subcutaneous injection of clonidine 2 µg/kg (SC clonidine). The primary outcome was total venous plasma ropivacaine concentrations up to 6 h after the block. There were no significant differences in plasma ropivacaine concentrations between the control group and the clonidine group at any timepoint in the study, nor were there differences in either the mean maximum ropivacaine concentration ( Cmax) (1.99 µg/mL versus 2.05 µg/mL, P = 0.712) or the time to maximum concentration ( Tmax) (51.0 min versus 56.0 min, P = 0.537). The SC clonidine group also did not differ significantly from the controls ( Cmax 2.13 µg/mL versus 1.99 µg/mL, P = 0.424; Tmax 43.5 min versus 51.0 min, P = 0.201). Plasma ropivacaine concentrations in the adrenaline group were significantly lower than the controls from 10 to 90 min ( P < 0.003 for each comparison), and the Cmax was less than that of the control group (1.36 µg/mL versus 1.99 µg/mL, P < 0.001) with a longer Tmax (103.5 min versus 51.0 min, P = 0.001). These findings indicate that clonidine at a concentration of 1.35 µg/mL added to ropivacaine for TAP blocks did not produce a reduction in plasma ropivacaine concentrations. This suggests a lack of vasoconstrictor effect during TAP blocks. Further studies should evaluate whether vasoconstriction occurs when clonidine is used at higher concentrations or for other blocks.

Obstructive sleep apnoea and anaesthesia.

Upper airway obstruction is common during both anaesthesia and sleep, as a result of loss of muscle tone present during wakefulness. Patients with obstructive sleep apnoea (OSA) are vulnerable during anaesthesia and sedation as the effects of loss of wakefulness are compounded by drug-induced depression of muscle activity and of arousal responses, so that they cannot respond to asphyxia. Conversely, those with 'difficult' airways during anaesthesia, either because of problems with maintenance of airway patency without tracheal intubation or because intubation itself is problematic, are at increased risk of OSA. These relationships have clinical importance. On the one hand identification of patients with OSA forewarns the anaesthetist of potential difficulty with airway maintenance intra- and postoperatively, influencing choice of anaesthetic technique and postoperative nursing environment. On the other hand difficulty with airway maintenance during anaesthesia should prompt further investigation for the possibility of OSA.