Impact of short-acting vs. standard anaesthetic agents on obstructive sleep apnoea: a randomised,controlled, triple-blind trial

Sleep apnoea is associated with negative outcomes following general anaesthesia. Current recommendations suggest using short-acting anaesthetic agents in preference to standard agents to reduce this risk, but there is currently no evidence to support this. This randomised controlled triple-blind trial tested the hypothesis that a combination of short-acting agents (desflurane-remifentanil) would reduce the postoperative impact of general anaesthesia on sleep apnoea severity compared with standard agents (sevoflurane-fentanyl). Sixty patients undergoing hip arthroplasty under general anaesthesia were randomised to anaesthesia with desflurane-remifentanil or sevoflurane-fentanyl. Respiratory polygraphy was performed before surgery and on the first and third postoperative nights. The primary outcome was the supine apnoea-hypopnoea index on the first postoperative night. Secondary outcomes were the supine apnoea-hypopnoea index on the third postoperative night, and the oxygen desaturation index on the first and third postoperative nights. Additional outcomes included intravenous morphine equivalent consumption and pain scores on postoperative days 1, 2 and 3. Pre-operative sleep study data were similar between groups. Mean (95%CI) values for the supine apnoea-hypopnoea index on the first postoperative night were 18.9 (12.7–25.0) and 21.4 (14.2–28.7) events.h⁻¹, respectively, in the short-acting and standard anaesthesia groups (p = 0.64). Corresponding values on the third postoperative night were 28.1 (15.8–40.3) and 38.0 (18.3–57.6) events.h⁻¹ (p = 0.34). Secondary sleep- and pain-related outcomes were generally similar in the two groups. In conclusion, short-acting anaesthetic agents did not reduce the impact of general anaesthesia on sleep apnoea severity compared with standard agents. These data should prompt an update of current recommendations.     

Cardiovascular risk markers in obstructive sleep apnoea syndrome and correlation with obesity

BACKGROUND: High C-reactive protein (CRP) and homocysteine levels are risk factors for cardiovascular disease. Some, but not all, previous studies have reported increased levels of CRP and homocysteine in patients with obstructive sleep apnoea syndrome (OSAS). A study was undertaken to investigate the levels of these factors in carefully selected patients with OSAS and matched normal controls. METHODS: CRP and homocysteine levels were measured in 110 subjects following polysomnography (PSG). Non-OSAS patients (group 1) were compared with two patient groups (mild/moderate OSAS (group 2) and severe OSAS (group 3)) group-matched for body mass index (BMI), and a fourth group of patients with severe OSAS who were more obese (group 4). All were free of other disease and similar in age, smoking habits and cholesterol levels. 50 suitable patients were commenced on continuous positive airway pressure (CPAP) treatment after PSG and 49 were reassessed 6 weeks later. RESULTS: CRP levels were similar in groups 1, 2 and 3 (median (interquartile range (IQR)) 1.11 (0.76-2.11) mg/l vs 1.82 (1.20-3.71) mg/l vs 2.20 (1.16-3.59) mg/l; p=0.727, Kruskal-Wallis test), but were significantly higher in group 4 than in the other groups (5.36 (2.42-9.17) mg/l, p<0.05 by individual group comparisons). In multivariate analysis of all subjects, BMI was an independent predictor for CRP levels (beta=0.221; p=0.006) but apnoea-hypopnoea index and other measures of OSAS were not. There was no difference in homocysteine levels between all four groups (p=0.1). CPAP did not alter CRP (2.29 (1.32-4.10) vs 2.84 (1.13-5.40) mg/l; p=0.145) or homocysteine levels (8.49 (3.66) vs 9.90 (4.72) micromol/l; p=0.381). CONCLUSION: CRP and homocysteine levels are not associated with OSAS severity in men but CRP is independently associated with obesity.     

Sleep . 8: paediatric obstructive sleep apnoea

In the past 25 years there has been increasing recognition of obstructive sleep apnoea (OSA) as a common condition of childhood. Morbidity includes impairment of growth, cardiovascular complications, learning impairment, and behavioural problems. Diagnosis and treatment of this condition in children differs in many respects from that in adults. We review here the key features of paediatric OSA, highlighting differences from adult OSA, and suggest future directions for research.     

Erythropoietin concentrations in obstructive sleep apnoea.

Eight patients with obstructive sleep apnoea and a normal haemoglobin concentration underwent nocturnal studies during which oxyhaemoglobin saturation was recorded continuously with an ear oximeter and serum erythropoietin concentration was measured hourly by means of a radioimmunoassay. Serum erythropoietin concentrations remained within the normal range throughout the study despite falls in oxyhaemaglobin saturation in individuals to 33-78%. There was no relation between the degree of nocturnal hypoxaemia and serum erythropoietin concentrations. The brief cyclical episodes of hypoxaemia typical of obstructive sleep apnoea may not be a sufficient stimulus for erythropoietin secretion.     

Randomised controlled crossover trial of humidified continuous positive airway pressure in mild obstructive sleep apnoea

BACKGROUND: It is unclear whether continuous positive airway pressure (CPAP), the treatment of choice for severe obstructive sleep apnoea (OSA), is effective at improving outcomes in mild OSA. METHODS: To help define the role of humidified CPAP in mild OSA, a randomised crossover study was undertaken of patients with an apnoea hypopnoea index (AHI) of 5-30/hour. Subjective sleepiness, objective wakefulness, mood, reaction time, and quality of life were measured at baseline, after 3 weeks treatment with humidified CPAP and 3 weeks sham CPAP (2 week washout). RESULTS: Twenty nine of 31 enrolled patients (age 25-67 years, seven women, mean (SD) body mass index 31.5 (6) kg/m2) completed the protocol. Humidified CPAP improved polysomnographic indices of OSA and Epworth Sleepiness Scale (2.4 points (95% CI 0.6 to 4.2)). Objective wakefulness (modified maintenance of wakefulness test) showed a trend towards improvement (5.2 minutes (95% CI -0.6 to 11)). Mood (Hospital Anxiety and Depression Scale), quality of life (SF 36, Functional Outcomes of Sleep Questionnaire), and reaction times (Psychomotor Vigilance Task) were not improved more than sham CPAP. Compliance with humidified and sham CPAP both averaged 4.9 hours/night. Placebo effects were evident in many outcomes and there was no clear treatment preference. CONCLUSIONS: Humidified CPAP improves subjective sleepiness and possibly objective wakefulness but not reaction times, quality of life, or mood. These results do not support the routine use of CPAP in all patients with mild OSA, but offers some support for the trialling of CPAP in those with severe sleepiness.     

Orthopaedic fractures: trends in randomised controlled trials

Aim: To ascertain and describe the number and epidemiology of randomised controlled trials (RCTs) focused on orthopaedic fractures. Methods: A sensitive literature search was carried out for the period 1966–May 1999. Labels were applied to each identified RCT to indicate the fracture type, and the main type of intervention. Results: 648 RCTs related to surgery of which 123 focused on adjuvant therapies and 88 related mainly to anaesthesia, analgesia, and radiography. The number of trials have increased exponentially with time so that the present decade has seen more RCTs published than all the other years added together. Conclusion: There is clearly an encouraging trend in the number of RCTs published. However there is a need to ensure that trials are on fracture types where there is most need for guidance. This growing evidence base should fuel systematic reviews and clinical guidelines within orthopaedics.     

Challenging issues in randomised controlled trials

What this topic is aboutRandomised controlled trials (RCTs) are the most rigorous way of determining whether a cause–effect relation exists between treatment and outcome and are an integral component in the hierarchy of evidence which guide current clinical practice. Whether ensuring the success of a RCT or interpreting the medical literature, it is important to understand the key components of RCT design to assess their quality and therefore the weight which should be attributed to its findings. This article will highlight some of these key components by using a number of ongoing trauma studies being co-ordinated by the Australian and New Zealand Intensive Care Research Centre, Monash University.Common problems and challengesThe quality of many RCTs could be improved by avoiding some common pitfalls, such as (i) unclear hypotheses and multiple objectives, (ii) poor selection of endpoints, (iii) inappropriate subject selection criteria, (iv) non-clinically relevant or feasible treatment/intervention regimens, (v) inadequate randomisation, stratification, blinding, (vi) lack of stratification in small RCTs (vii) inadequate blinding of trials, (viii) insufficient sample size/power, (ix) failure to use intention to treat analysis and (x) failure to anticipate common practical problems encountered during the conduct of a RCT.Tips for researchersThe RCTs most likely to be funded and/or be of high quality always address these issues.     

The analysis of 168 randomised controlled trials to test data integrity

The purpose of this study was to use some statistical methods to assess if randomised controlled trials (RCTs) published by one particular author (Fujii) contained data of unusual consistency. I searched seven electronic databases, retrieving 168 RCTs published by this author between 1991 and July 2011. I extracted rates for categorical variables and means (SDs) for continuous variables, and compared these published distributions with distributions that would be expected by chance. The published distributions of 28/33 variables (85%) were inconsistent with the expected distributions, such that the likelihood of their occurring ranged from 1 in 25 to less than 1 in 1 000 000 000 000 000 000 000 000 000 000 000 (1 in 10(33)), equivalent to p values of 0.04 to < 1 × 10(-33) , respectively. In 141 human studies, 13/13 published continuous variable distributions were inconsistent with expected, their likelihoods being: weight < 1 in 10(33) ; age < 1 in 10(33) ; height < 1 in 10(33) ; last menstrual period 1 in 4.5 × 10(15) ; baseline blood pressure 1 in 4.2 × 10(5) ; gestational age 1 in 28; operation time < 1 in 10(33) ; anaesthetic time < 1 in 10(33) ; fentanyl dose 1 in 6.3 × 10(8) ; operative blood loss 1 in 5.6 × 10(9) ; propofol dose 1 in 7.7 × 10(7) ; paracetamol dose 1 in 4.4 × 10(2) ; uterus extrusion time 1 in 33. The published distributions of 7/11 categorical variables in these 141 studies were inconsistent with the expected, their likelihoods being: previous postoperative nausea and vomiting 1 in 2.5 × 10(6) ; motion sickness 1 in 1.0 × 10(4) ; male or female 1 in 140; antihypertensive drug 1 in 25; postoperative headache 1 in 7.1 × 10(10) ; postoperative dizziness 1 in 1.6 × 10(6) ; postoperative drowsiness 1 in 3.8 × 10(4) . Distributions for individual RCTs were inconsistent with the expected in 96/134 human studies by Fujii et al. that reported more than two continuous variables, their likelihood ranging from 1 in 22 to 1 in 140 000 000 000 (1 in 1.4 × 10(11)), compared with 12/139 RCTs by other authors. In 26 canine studies, the distributions of 8/9 continuous variables were inconsistent with the expected, their likelihoods being: right atrial pressure < 1 in 10(33) ; diaphragmatic stimulation (100 Hz) < 1 in 10(33) ; pulmonary artery occlusion pressure < 1 in 10(33) ; diaphragmatic stimulation (20 Hz) < 1 in 10(33) ; heart rate 1 in 6.3 × 10(10) ; mean pulmonary artery pressure 1 in 2.2 × 10(14) ; mean arterial pressure 1 in 6.3 × 10(7) ; cardiac output 1 in 110. Distributions were inconsistent with the expected in 21/24 individual canine studies that reported more than two continuous variables, their likelihood ranging from 1 in 345 to 1 in 51 000 000 000 000 (1 in 5.1 × 10(13)).     

Uvulopalatopharyngoplasty in severe idiopathic obstructive sleep apnoea syndrome.

Eleven patients with severe obstructive sleep apnoea syndrome, which was fully reversed by treatment with nasal continuous positive airways pressure, underwent uvulopalatopharyngoplasty. All patients were followed for at least 12 months after surgery. One patient with large tonsils was cured. Of the remaining 10 patients, two showed minimal objective improvement at 12 months and the rest were unchanged. Four patients subsequently developed cardiac failure due to obstructive sleep apnoea. Thus uvulopalatopharyngoplasty was not effective in these patients with severe idiopathic obstructive sleep apnoea syndrome.     

Uvulopalatorrhaphy in a case of obstructive sleep apnoea.

A reversible uvulopalatorrhaphy is reported in a case of obstructive sleep apnoea. The patient had an abnormally long uvula but no skeletal abnormality.     

Minitracheotomy: a simple alternative to tracheostomy in obstructive sleep apnoea.

A patient with obstructive sleep apnoea sufficiently severe to cause papilloedema was managed temporarily with a minitracheotomy. This allowed arterial oxygen saturation to return to normal while he lost weight, before surgery for his enlarged tonsills.     

False individual patient data and zombie randomised controlled trials submitted to Anaesthesia

Concerned that studies contain false data, I analysed the baseline summary data of randomised controlled trials when they were submitted to Anaesthesia from February 2017 to March 2020. I categorised trials with false data as ‘zombie’ if I thought that the trial was fatally flawed. I analysed 526 submitted trials: 73 (14%) had false data and 43 (8%) I categorised zombie. Individual patient data increased detection of false data and categorisation of trials as zombie compared with trials without individual patient data: 67/153 (44%) false vs. 6/373 (2%) false; and 40/153 (26%) zombie vs. 3/373 (1%) zombie, respectively. The analysis of individual patient data was independently associated with false data (odds ratio (95% credible interval) 47 (17–144); p = 1.3 × 10⁻¹²) and zombie trials (odds ratio (95% credible interval) 79 (19–384); p = 5.6 × 10⁻⁹). Authors from five countries submitted the majority of trials: China 96 (18%); South Korea 87 (17%); India 44 (8%); Japan 35 (7%); and Egypt 32 (6%). I identified trials with false data and in turn categorised trials zombie for: 27/56 (48%) and 20/56 (36%) Chinese trials; 7/22 (32%) and 1/22 (5%) South Korean trials; 8/13 (62%) and 6/13 (46%) Indian trials; 2/11 (18%) and 2/11 (18%) Japanese trials; and 9/10 (90%) and 7/10 (70%) Egyptian trials, respectively. The review of individual patient data of submitted randomised controlled trials revealed false data in 44%. I think journals should assume that all submitted papers are potentially flawed and editors should review individual patient data before publishing randomised controlled trials.