Music to prevent deliriUm during neuroSurgerY (MUSYC): a single-centre, prospective randomised controlled trial.

OBJECTIVES: Delirium is a serious complication following neurosurgical procedures. We hypothesise that the beneficial effect of music on a combination of delirium-eliciting factors might reduce delirium incidence following neurosurgery and subsequently improve clinical outcomes. DESIGN: Prospective randomised controlled trial. SETTING: Single centre, conducted at the neurosurgical department of the Erasmus Medical Center, Rotterdam, the Netherlands. PARTICIPANTS: Adult patients undergoing craniotomy were eligible. INTERVENTIONS: Patients in the intervention group received preferred recorded music before, during and after the operation until day 3 after surgery. Patients in the control group were treated according to standard of clinical care. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was presence or absence of postoperative delirium within the first 5 postoperative days measured with the Delirium Observation Screening Scale (DOSS) and, in case of a daily mean score of 3 or higher, a psychiatric evaluation with the latest Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria. Secondary outcomes included anxiety, heart rate variability (HRV), depth of anaesthesia, delirium severity and duration, postoperative complications, length of stay and location of discharge. RESULTS: We enrolled 189 patients (music=95, control=94) from July 2020 through September 2021. Delirium, as assessed by the DOSS, was less common in the music (n=11, 11.6%) than in the control group (n=21, 22.3%, OR:0.49, p=0.048). However, after DSM-5 confirmation, differences in delirium were not significant (4.2% vs 7.4%, OR:0.47, p=0.342). Moreover, music increased the HRV (root mean square of successive differences between normal heartbeats, p=0.012). All other secondary outcomes were not different between groups. CONCLUSION: Our results support the efficacy of music in reducing the incidence of delirium after craniotomy, as found with DOSS but not after DSM-5 confirmation, substantiated by the effect of music on preoperative autonomic tone. Delirium screening tools should be validated and the long-term implications should be evaluated after craniotomy. TRIAL REGISTRATION NUMBER: Trialregister.nl: NL8503 and ClinicalTrials.gov: NCT04649450.

Prognostic factors for chronic post-surgical pain after lung and pleural surgery: a systematic review with meta-analysis, meta-regression and trial sequential analysis.

Chronic post-surgical pain is known to be a common complication of thoracic surgery and has been associated with a lower quality of life, increased healthcare utilisation, substantial direct and indirect costs, and increased long-term use of opioids. This systematic review with meta-analysis aimed to identify and summarise the evidence of all prognostic factors for chronic post-surgical pain after lung and pleural surgery. Electronic databases were searched for retrospective and prospective observational studies as well as randomised controlled trials that included patients undergoing lung or pleural surgery and reported on prognostic factors for chronic post-surgical pain. We included 56 studies resulting in 45 identified prognostic factors, of which 16 were pooled with a meta-analysis. Prognostic factors that increased chronic post-surgical pain risk were as follows: higher postoperative pain intensity (day 1, 0-10 score), mean difference (95%CI) 1.29 (0.62-1.95), p < 0.001; pre-operative pain, odds ratio (95%CI) 2.86 (1.94-4.21), p < 0.001; and longer surgery duration (in minutes), mean difference (95%CI) 12.07 (4.99-19.16), p < 0.001. Prognostic factors that decreased chronic post-surgical pain risk were as follows: intercostal nerve block, odds ratio (95%CI) 0.76 (0.61-0.95) p = 0.018 and video-assisted thoracic surgery, 0.54 (0.43-0.66) p < 0.001. Trial sequential analysis was used to adjust for type 1 and type 2 errors of statistical analysis and confirmed adequate power for these prognostic factors. In contrast to other studies, we found that age had no significant effect on chronic post-surgical pain and there was not enough evidence to conclude on sex. Meta-regression did not reveal significant effects of any of the study covariates on the prognostic factors with a significant effect on chronic post-surgical pain. Expressed as grading of recommendations, assessment, development and evaluations criteria, the certainty of evidence was high for pre-operative pain and video-assisted thoracic surgery, moderate for intercostal nerve block and surgery duration and low for postoperative pain intensity. We thus identified actionable factors which can be addressed to attempt to reduce the risk of chronic post-surgical pain after lung surgery.

Delirium in neurosurgery: a systematic review and meta-analysis.

Delirium is a frequent occurring complication in surgical patients. Nevertheless, a scientific work-up of the clinical relevance of delirium after intracranial surgery is lacking. We conducted a systematic review (CRD42020166656) to evaluate the current diagnostic work-up, incidence, risk factors and health outcomes of delirium in this population. Five databases (Embase, Medline, Web of Science, PsycINFO, Cochrane Central) were searched from inception through March 31st, 2021. Twenty-four studies (5589 patients) were included for qualitative analysis and twenty-one studies for quantitative analysis (5083 patients). Validated delirium screening tools were used in 70% of the studies, consisting of the Confusion Assessment Method (intensive care unit) (45%), Delirium Observation Screening Scale (5%), Intensive Care Delirium Screening Checklist (10%), Neelon and Champagne Confusion Scale (5%) and Nursing Delirium Screening Scale (5%). Incidence of post-operative delirium after intracranial surgery was 19%, ranging from 12 to 26% caused by variation in clinical features and delirium assessment methods. Meta-regression for age and gender did not show a correlation with delirium. We present an overview of risk factors and health outcomes associated with the onset of delirium. Our review highlights the need of future research on delirium in neurosurgery, which should focus on optimizing diagnosis and assessing prognostic significance and management.

Music to prevent deliriUm during neuroSurgerY (MUSYC) Clinical trial: a study protocol for a randomised controlled trial.

INTRODUCTION: Delirium is a neurocognitive disorder characterised by an acute and temporary decline of mental status affecting attention, awareness, cognition, language and visuospatial ability. The underlying pathophysiology is driven by neuroinflammation and cellular oxidative stress.Delirium is a serious complication following neurosurgical procedures with a reported incidence varying between 4% and 44% and has been associated with increased length of hospital stay, increased amount of reoperations, increased costs and mortality.Perioperative music has been reported to reduce preoperative anxiety, postoperative pain and opioid usage, and attenuates stress response caused by surgery. We hypothesize that this beneficial effect of music on a combination of delirium eliciting factors might reduce delirium incidence following neurosurgery and subsequently improve clinical outcomes. METHODS: This protocol concerns a single-centred prospective randomised controlled trial with 6 months follow-up. All adult patients undergoing a craniotomy at the Erasmus Medical Center in Rotterdam are eligible. The music group will receive recorded music through an overear headphone before, during and after surgery until postoperative day 3. Patients can choose from music playlists, offered based on music importance questionnaires administered at baseline. The control group will receive standard of clinical careDelirium is assessed by the Delirium Observation Scale and confirmed by a delirium-expert psychiatrist according to the DSM-5 criteria. Risk factors correlated with the onset of delirium, such as cognitive function at baseline, preoperative anxiety, perioperative medication use, depth of anaesthesia and postoperative pain, and delirium-related health outcomes such as length of stay, daily function, quality of life (ie, EQ-5D, EORTC questionnaires), costs and cost-effectiveness are collected. ETHICS AND DISSEMINATION: This study is being conducted in accordance with the Declaration of Helsinki. The Medical Ethics Review Board of Erasmus University Medical Center Rotterdam, The Netherlands, approved this protocol. Results will be disseminated via peer-reviewed scientific journals and conference presentations. TRIAL REGISTRATION NUMBERS: NL8503 and NCT04649450.

Implementation of music in the perioperative standard care of colorectal surgery: study protocol of the IMPROVE Study.

INTRODUCTION: Perioperative music intervention has been proven effective in reducing anxiety, pain, neurohormonal stress response and medication requirement. Unfortunately, there is a gap between new effective interventions and their (interventions) integration in standard care protocols. The aim of this preimplementation and postimplementation study is to investigate the adherence to a music intervention in a tailored, multilevel, systematic implementation strategy and the initial impact of the implementation on postoperative pain in patients undergoing colorectal surgery. METHODS AND DESIGN: A monocentre prospective preimplementation and postimplementation study was set up using The Consolidated Framework for Implementation Research to conduct a systematic implementation of music intervention in three phases. Primary outcomes are adherence to the music intervention and the initial impact of the music intervention implementation on postoperative pain scores on the first postoperative day. At least 100 patients will be included in the study. Secondary outcomes include adherence to the implementation strategy, penetration of music intervention in the standard care, assessment of the determinants for implementation, impact of the implemented music intervention on pain during the entire admission, anxiety, medication usage, complications, hospital and intensive care unit (ICU) length of stay. ETHICS AND DISSEMINATION: The Medical Ethics Review Board of Erasmus MC University Medical Centre Rotterdam, The Netherlands, has approved this protocol. The study is being conducted in accordance with the Declaration of Helsinki. Results of this trial will be published in peer-reviewed scientific journals and conference presentations. TRIAL REGISTRATION: Dutch Trial Register NL8071.

A systematic review and trial sequential analysis of intravenous vs. oral peri-operative paracetamol.

Postoperative pain might be different after intravenous vs. oral paracetamol. We systematically reviewed randomised controlled trials in patients >15 years that compared intravenous with oral paracetamol for postoperative pain. We identified 14 trials with 1695 participants. There was inconclusive evidence for an effect of route of paracetamol administration on postoperative pain at 0-2 h (734 participants), 2-6 h (766 participants), 6-24 h (1115 participants) and >24 h (248 participants), with differences in standardised mean (95%CI) pain scores for intravenous vs. oral of -0.17 (-0.45 to 0.10), -0.09 (-0.24 to 0.06), 0.06 (-0.12 to 0.23) and 0.03 (-0.22 to 0.28), respectively. Trial sequential analyses suggested that a total of 3948 participants would be needed to demonstrate a meaningful difference in pain or its absence at 0-2 h. There were no differences in secondary outcomes. Intravenous paracetamol is more expensive than oral paracetamol. Substitution of oral paracetamol in half the patients given intravenous paracetamol in our hospital would save around £ 38,711 (€ 43,960 or US$ 47,498) per annum.

A systematic review of phenylephrine vs. noradrenaline for the management of hypotension associated with neuraxial anaesthesia in women undergoing caesarean section.

Phenylephrine is recommended for the management of hypotension after spinal anaesthesia in women undergoing caesarean section. Noradrenaline, an adrenergic agonist with weak ß-adrenergic activity, has been reported to have a more favourable haemodynamic profile than phenylephrine. However, there are concerns that noradrenaline may be associated with a higher risk of fetal acidosis, defined as an umbilical artery pH < 7.20. We performed a systematic review of trials comparing noradrenaline with phenylephrine, concentrating on primary outcomes of fetal acidosis and maternal hypotension. We identified 13 randomised controlled trials including 2002 patients. Heterogeneity among the studies was high, and there were too few data to calculate a pooled effect estimate. Fetal acidosis was assessed in four studies that had a low risk of bias and a low risk of confounding, that is, studies which used a prophylactic vasopressor and where women received the allocated vasopressor only. There were no significant differences between these studies. No significant differences were observed for hypotension. Two trials found a significantly lower incidence of bradycardia when using noradrenaline. Cardiac output was significantly higher after noradrenaline in two of three studies. For other secondary outcomes including nausea, vomiting and Apgar scores at 1 and 5 min, no studies found significant differences. The evidence so far is too limited to support an advantage of noradrenaline over phenylephrine. Concerns of a deleterious effect of noradrenaline on fetal blood gas status cannot currently be assuaged by the available data from randomised controlled studies.

Variation in the practice of tracheal intubation in Europe after traumatic brain injury: a prospective cohort study.

Traumatic brain injury patients frequently undergo tracheal intubation. We aimed to assess current intubation practice in Europe and identify variation in practice. We analysed data from patients with traumatic brain injury included in the prospective cohort study collaborative European neurotrauma effectiveness research in traumatic brain injury (CENTER-TBI) in 45 centres in 16 European countries. We included patients who were transported to hospital by emergency medical services. We used mixed-effects multinomial regression to quantify the effects on pre-hospital or in-hospital tracheal intubation of the following: patient characteristics; injury characteristics; centre; and trauma system characteristics. A total of 3843 patients were included. Of these, 1322 (34%) had their tracheas intubated; 839 (22%) pre-hospital and 483 (13%) in-hospital. The fit of the model with only patient characteristics predicting intubation was good (Nagelkerke R2 64%). The probability of tracheal intubation increased with the following: younger age; lower pre-hospital or emergency department GCS; higher abbreviated injury scale scores (head and neck, thorax and chest, face or abdomen abbreviated injury score); and one or more unreactive pupils. The adjusted median odds ratio for intubation between two randomly chosen centres was 3.1 (95%CI 2.1-4.3) for pre-hospital intubation, and 2.7 (95%CI 1.9-3.5) for in-hospital intubation. Furthermore, the presence of an anaesthetist was independently associated with more pre-hospital intubation (OR 2.9, 95%CI 1.3-6.6), in contrast to the presence of ambulance personnel who are allowed to intubate (OR 0.5, 95%CI 0.3-0.8). In conclusion, patient and injury characteristics are key drivers of tracheal intubation. Between-centre differences were also substantial. Further studies are needed to improve the evidence base supporting recommendations for tracheal intubation.

Intrathecal catheterisation after observed accidental dural puncture in labouring women: update of a meta-analysis and a trial-sequential analysis.

BACKGROUND: Our meta-analysis from 2013 showed that inserting a catheter intrathecally after an observed accidental dural puncture can reduce the need for epidural blood patch in labouring women requesting epidural analgesia. We updated our conventional meta-analysis and added a trial-sequential analysis (TSA). METHODS: A systematic literature search was conducted to identify studies that compared inserting the catheter intrathecally with an epidural catheter re-site or with no intervention. The extracted data were pooled and the risk ratio (RR) and 95% confidence interval (95%CI) for the incidence of post-dural puncture headache (PDPH) was calculated, using the random effects model. A contour-enhanced funnel plot was constructed. A TSA was performed and the cumulative Z score, monitoring and futility boundaries were constructed. RESULTS: Our search identified 13 studies, reporting on 1653 patients, with a low risk of bias. The RR for the incidence of PDPH was 0.82 (95%CI 0.71 to 0.95) and the RR for the need for epidural blood patch was 0.62 (95%CI 0.49 to 0.79); heterogeneity of both analyses was high. The TSA showed that the monitoring or futility boundaries were not crossed, indicating insufficient data to exclude a type I error of statistical analysis. Contour-enhanced funnel plots were symmetric, suggesting no publication bias. CONCLUSIONS: Conventional meta-analyses showed for the first time that intrathecal catheterisation can reduce the incidence of PDPH. However, TSA did not corroborate this finding. Despite increasing use in clinical practice there is no firm evidence on which to base a definite conclusion.

Dural puncture epidural versus conventional epidural block for labor analgesia: a systematic review of randomized controlled trials.

INTRODUCTION: Dural puncture epidural (DPE) analgesia is a modification of conventional epidural analgesia that involves the intentional puncture of the dura with a spinal needle through the needle placed in the epidural space, without a medication being injected intrathecally. There have been contradictory findings regarding better analgesia and better block quality. METHODS: A systematic literature search was done to identify randomized controlled trials (RCT) comparing DPE with epidural analgesia. The risk of bias was assessed with the Cochrane tool. Risk ratio and 95% confidence intervals were calculated. RESULTS: Five RCTs including 581 patients were identified. One RCT on caesarean section was excluded. Single studies suggested slightly better analgesia by finding a median time to achieve sufficient analgesia of two minutes less in the DPE group, a higher number of women having a pain score <10/100 at 20 min, a reduction in the number of epidural top-ups and better sacral spread. The studies did not show a difference between DPE and epidural analgesia for catheter replacement or manipulation rates, the incidence of intravascular placement or unilateral block. CONCLUSION: There is a lack of clear evidence on either the benefits or therisks of the DPE technique, such that a recommendation for or against its routine use is premature. Two of the three studies showing a beneficial effect of DPE came from the same institution and replication of the findings by other groups is warranted.

Effect of intravenous dexamethasone on postoperative pain after spinal anaesthesia - a systematic review with meta-analysis and trial sequential analysis.

There are data suggesting that intravenous dexamethasone has an effect on postoperative analgesia when given during single-shot spinal anaesthesia. However, the research literature is equivocal. We performed a systematic literature search followed by conventional meta-analysis (random effects model). We used trial sequential analysis to control for type-1 and -2 statistical errors. We also performed a leave-one-out meta-analysis for our primary outcome, the consumption of intravenous morphine in the first 24 postoperative hours. We applied the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to rate the level of evidence. We obtained data from 1133 patients, reported in 17 trials. Reporting quality was high, with low risk of bias. Dexamethasone use was associated with a significant reduction in 24-h morphine consumption, the mean difference (95%CI) being -4.01 (-5.01 to -3.01) mg, 6 trials, 326 participants, I2 = 0%. Trial sequential analysis showed that there was firm evidence for the primary outcome, and leave-one-out meta-analysis showed that our result was not driven by one single trial. The GRADE evaluation showed a high level of evidence, suggesting that further studies are unlikely to alter the result. The time to first analgesic request (95%CI) was significantly prolonged by 86.62 (10.62-162.62) min, I2 = 93%, in the dexamethasone group. For other secondary outcomes including number of patients requiring rescue analgesia, or visual analogue scale pain scores, we found no evidence of a significant difference between the treatment arms. We report a high level of evidence that intravenous dexamethasone improves postoperative analgesia after spinal anaesthesia.

Propofol sedation without endotracheal intubation is safe for endoscopic submucosal dissection in the esophagus and stomach.

Background: Endoscopic submucosal dissection (ESD) for early esophageal and stomach cancer is usually performed under general anesthesia. However, propofol sedation without endotracheal intubation has been suggested as a viable alternative. Objective: The objective of this study was to evaluate the safety of propofol sedation without endotracheal intubation during ESD in the upper gastrointestinal tract. Methods: We performed a retrospective cohort study of patients who underwent ESD for upper gastrointestinal tumors with propofol-remifentanil analgosedation in a tertiary referral center in the Netherlands between October 2013 and February 2018. Primary endpoints were the rates of intraprocedural endoscopy- and anesthesia-related complications. Secondary endpoints were the postprocedural complication rates within 30 days and endotracheal intubation conversion rates. Results: Of 88 patients, intraprocedural ESD-related complications occurred in three patients (3.4%). Intraprocedural anesthesia-related complications occurred in two patients (2.3%), one of whom required conversion to endotracheal intubation. Postprocedural ESD-related complications occurred in 14 patients (15.9%), and minor postprocedural complications occurred in two patients (2.3%). Eighty-two (93.2%) patients were discharged within one day after ESD. No patient was readmitted for anesthesia-related complications. Conclusion: Propofol-based sedation without endotracheal intubation is safe for ESD procedures in the esophagus and stomach with low anesthesia-related complication rates and short hospital stay.

Ephedrine versus phenylephrine as a vasopressor for spinal anaesthesia-induced hypotension in parturients undergoing high-risk caesarean section: meta-analysis, meta-regression and trial sequential analysis.

BACKGROUND: Phenylephrine is the preferred vasopressor for the prevention and treatment of spinal anaesthesia-induced hypotension during caesarean section, because studies on low-risk elective patients found it to have a less detrimental effect on umbilical artery pH compared with ephedrine. However, limited data exist from high-risk parturients and parturients with uteroplacental insufficiency. METHODS: We systematically searched for randomised, controlled, double-blinded trials of these two vasopressors in high-risk caesarean sections. We applied conventional meta-analysis, trial sequential analysis, computing the required information size that would exclude type I and II errors, contour-enhanced funnel plot testing for publication bias, meta-regression to assess the dose-response relationship, and the Grading of Recommendations Assessment, Development, and Evaluation system (GRADE). The incidence of fetal acidosis (umbilical arterial pH <7.2) was the primary outcome. RESULTS: Eight trials (712 patients) with low risk of bias were identified. Pooling six studies of patients with preeclampsia and other reasons for fetal compromise, as well as subgroup analysis of the preeclampsia studies, revealed no significant differences in the incidence of fetal acidosis. Trial sequential analysis showed that the required information size was not reached. The funnel plot was not suggestive of publication bias. Meta-regression showed no dose-response relationship. The GRADE score was moderate quality. CONCLUSIONS: Despite several studies and a large number of patients there was insufficient evidence to make a recommendation for choice of vasopressor in high-risk caesarean section. Trials with adequate power to detect differences in the incidence of fetal acidosis between ephedrine and phenylephrine are required to provide evidence-based guidance.