An international multidisciplinary consensus statement on fasting before procedural sedation in adults and children.

The multidisciplinary International Committee for the Advancement of Procedural Sedation presents the first fasting and aspiration prevention recommendations specific to procedural sedation, based on an extensive review of the literature. These were developed using Delphi methodology and assessment of the robustness of the available evidence. The literature evidence is clear that fasting, as currently practiced, often substantially exceeds recommended time thresholds and has known adverse consequences, for example, irritability, dehydration and hypoglycaemia. Fasting does not guarantee an empty stomach, and there is no observed association between aspiration and compliance with common fasting guidelines. The probability of clinically important aspiration during procedural sedation is negligible. In the post-1984 literature there are no published reports of aspiration-associated mortality in children, no reports of death in healthy adults (ASA physical status 1 or 2) and just nine reported deaths in adults of ASA physical status 3 or above. Current concerns about aspiration are out of proportion to the actual risk. Given the lower observed frequency of aspiration and mortality than during general anaesthesia, and the theoretical basis for assuming a lesser risk, fasting strategies in procedural sedation can reasonably be less restrictive. We present a consensus-derived algorithm in which each patient is first risk-stratified during their pre-sedation assessment, using evidence-based factors relating to patient characteristics, comorbidities, the nature of the procedure and the nature of the anticipated sedation technique. Graded fasting precautions for liquids and solids are then recommended for elective procedures based upon this categorisation of negligible, mild or moderate aspiration risk. This consensus statement can serve as a resource to practitioners and policymakers who perform and oversee procedural sedation in patients of all ages, worldwide.

The effect of sleep deprivation and disruption on DNA damage and health of doctors.

Observational studies have highlighted the detrimental health effects of shift work. The mechanisms through which acute sleep deprivation may lead to chronic disease have not been elucidated, but it is thought that increased DNA damage or decreased repair can lead to disease. The objective of this study was to examine the effects of acute sleep deprivation on DNA damage. This was a cross-sectional observational study on 49 healthy, full-time doctors. Baseline blood was sampled from each participant after three consecutive days of adequate sleep. Participants (n = 24) who were required to work overnight on-site had additional blood sampled on a morning after acute sleep deprivation. DNA damage and expression of DNA repair genes were quantified. Information on health, working patterns and sleep diaries were collected. Independent t-tests were used to compare differences between groups and standardised mean differences expressed as Cohen's d. Overnight on-site call participants had lower baseline DNA repair gene expression and more DNA breaks than participants who did not work overnight (d = 1.47, p = 0.0001; and 1.48, p = 0.0001, respectively). In overnight on-site call participants, after acute sleep deprivation, DNA repair gene expression was decreased (d = 0.90, p = 0.0001) and DNA breaks were increased (d = 0.87, p = 0.0018). Sleep deprivation in shift workers is associated with adverse health consequences. Increased DNA damage has been linked to the development of chronic disease. This study demonstrates that disrupted sleep is associated with DNA damage. Furthermore, larger prospective studies looking at relationships between DNA damage and chronic disease development are warranted, and methods to relieve, or repair, DNA damage linked to sleep deprivation should be investigated.

Comparison of target-controlled infusion and manual infusion for propofol anaesthesia in children.

BACKGROUND: One major criticism of prolonged propofol-based total i.v. anaesthesia (TIVA) in children is the prolonged recovery time. As target-controlled infusion (TCI) obviates the need to manually calculate the infusion rate, the use of TCI may better match clinical requirements, reduce propofol dose, and shorten recovery time. METHODS: Children of ASA grade 1, aged 1-12 yr, were recruited and randomly assigned to TCI or manual infusion. Children in the TCI group had propofol delivered by TCI. Children for manual infusion had a loading dose of 2.5 mg kg-1 with subsequent infusion rates of 15, 13, 11, 10, and 9 mg kg-1 h-1. Attending anaesthesiologists adjusted the propofol dosage to keep the Bispectral Index™ (BIS) between 40 and 60. RESULTS: Seventy-four children completed the study. The time taken to extubate the trachea after cessation of propofol was 15.1 (5.5) and 16.2 (6.1) min for children who had TCI and manual infusion, respectively (P=0.42). The mean propofol infusion rate was 16.7 [standard deviation (sd) 4.2] mg kg-1 h-1 in the TCI group and 14.6 (3.1) mg kg-1 h-1 in the manual infusion group (P=0.036). The percentage of time when BIS was >60 was significantly lower in the TCI than the manual infusion group [10.2% (18.4%) vs 23.2% (26.3%), P=0.016]. DISCUSSION: Use of TCI led to higher propofol doses but not prolonged recovery time in children compared with manual infusion. It was associated with a greater percentage of time when the BIS was in the desired range and it may be an easier method for titration of propofol administration during anaesthesia or sedation. CLINICAL TRIAL REGISTRATION: ChiCTR-IOD-16010147.

Pharmacokinetic and pharmacodynamic study of intranasal and intravenous dexmedetomidine.

BACKGROUND: Intranasal dexmedetomidine produces safe, effective sedation in children and adults. It may be administered by drops from a syringe or by nasal mucosal atomisation (MAD NasalTM). METHODS: This prospective, three-period, crossover, double-blind study compared the pharmacokinetic (PK) and pharmacodynamic (PD) profile of i.v. administration with these two different modes of administration. In each session each subject received 1 µg kg-1 dexmedetomidine, either i.v., intranasal with the atomiser or intranasal by drops. Dexmedetomidine plasma concentration and Ramsay sedation score were used for PK/PD modelling by NONMEM. RESULTS: The i.v. route had a significantly faster onset (15 min, 95% CI 15-20 min) compared to intranasal routes by atomiser (47.5 min, 95% CI 25-135 min), and by drops (60 min, 95%CI 30-75 min), (P<0.001). There was no significant difference in sedation duration across the three treatment groups (P=0.88) nor in the median onset time between the two modes of intranasal administration (P=0.94). A 2-compartment disposition model, with transit intranasal absorption and clearance driven by cardiac output using the well-stirred liver model, was the final PK model. Intranasal bioavailability was estimated to be 40.6% (95% CI 34.7-54.4%) and 40.7% (95% CI 36.5-53.2%) for atomisation and drops respectively. Sedation score was modelled via a sigmoidal Emax model driven by an effect compartment. The effect compartment had an equilibration half time 3.3 (95% CI 1.8-4.7) min-1, and the EC50 was estimated to be 903 (95% CI 450-2344) pg ml-1. CONCLUSIONS: There is no difference in bioavailability with atomisation or nasal drops. A similar degree of sedation can be achieved by either method. CLINICAL TRIAL REGISTRATION: HKUCTR-1617.

A comparison of two techniques for induction of anaesthesia with target-controlled infusion of propofol.

Induction of anaesthesia with target-controlled infusion of propofol may be achieved by stepwise increases in effect-site concentration until the patient loses consciousness (titration method), or by setting a high effect-site concentration target and observing the calculated effect-site concentration at loss of consciousness (standard method). When the estimated effect-site concentration at loss of consciousness is accurate, the difference between effect-site concentration at loss of consciousness and at recovery of consciousness should be small. This prospective, randomised, controlled trial was designed to compare this difference (effect-site concentration at loss of consciousness - effect-site concentration at recovery of consciousness) associated with the two techniques. Sixty-seven healthy patients undergoing elective hemithyroidectomy were recruited. Induction of anaesthesia was achieved using effect-site target-controlled infusion with the modified Marsh model and ke0 of 1.2 min-1 . The median (IQR [range]) difference between effect-site concentration at loss of consciousness and recovery of consciousness was significantly lower in patients in the titration group at 1.2 (0.8-1.5 [0.1-2.9]) µg.ml-1 compared with the standard group 2.1 (1.9-2.6 [0.2-3.6] µg.ml-1 ; p < 0.0001). There was a positive correlation between effect-site concentration at loss of, and recovery of, consciousness (R = 0.41, p = 0.016) in the titration group, which was not seen in the standard group (R = -0.15, p = 0.44). In conclusion, using the modified Marsh pharmacokinetic model, the titration method for target-controlled infusion propofol at induction of anaesthesia allows closer matching of propofol concentration to depth of anaesthesia than the standard method.

A pilot study of ultrasound evaluation of gastric emptying in patients with end-stage renal failure: a comparison with healthy controls.

This prospective study was designed to evaluate gastric volume and content in patients with renal failure and healthy controls after an overnight fast, immediately after a light meal and at 6 h after the meal. Thirty subjects in each group were recruited. At each scanning session, gastric antral cross-sectional area was measured in the supine recumbent and right lateral decubitus positions, and a qualitative assessment of gastric contents was made using the Perlas three-point grading system. Six hours after the meal, the mean (SD) antral cross-sectional area in the supine position was 471 (195) mm2 in patients with renal failure and 319 (106) mm2 in healthy controls (p = 0.028), whereas in the right lateral position it was 756 (320) and 521 (180) mm2 , respectively (p = 0.21). In terms of the qualitative assessments of gastric contents, all subjects had an empty stomach after an overnight fast. Five patients with renal failure and no controls had Perlas grade 2 images, indicating significant gastric contents, 6 h after a meal (p = 0.026). This study supports the use of bedside gastric ultrasound as a point-of-care test for patients with known risk factors for delayed gastric emptying.

A randomised controlled trial of oral chloral hydrate vs. intranasal dexmedetomidine before computerised tomography in children.

Chloral hydrate is commonly used to sedate children for painless procedures. Children may recover more quickly after sedation with dexmedetomidine, which has a shorter half-life. We randomly allocated 196 children to chloral hydrate syrup 50 mg.kg-1 and intranasal saline spray, or placebo syrup and intranasal dexmedetomidine spray 3 µg.kg-1 , 30 min before computerised tomography studies. More children resisted or cried after drinking chloral hydrate syrup than placebo syrup, 72 of 107 (67%) vs. 42 of 87 (48%), p = 0.009, but there was no difference after intranasal saline vs. dexmedetomidine, 49 of 107 (46%) vs. 40 of 87 (46%), p = 0.98. Sedation was satisfactory in 81 of 107 (76%) children after chloral hydrate and 64 of 87 (74%) children after dexmedetomidine, p = 0.74. Of the 173 children followed up for at least 4 h after discharge, 38 of 97 (39%) had recovered normal function after chloral hydrate and 32 of 76 (42%) after dexmedetomidine, p = 0.76. Six children vomited after chloral hydrate syrup and placebo spray vs. none after placebo syrup and dexmedetomidine spray, p = 0.03.

A comparison of intranasal dexmedetomidine for sedation in children administered either by atomiser or by drops.

Intranasal dexmedetomidine has been used successfully for sedation in children. A mucosal atomisation device delivers an atomised solution to the nasal mucosa which facilitates rapid and effective delivery of medication to the systemic circulation. We compared intranasal delivery of dexmedetomidine in a dose of 3 µg.kg(-1) by either atomiser or drops from a syringe in children < 3 years old undergoing transthoracic echocardiography. Two hundred and seventy-nine children were randomly assigned to one or other group. One hundred and thirty-seven children received dexmedetomidine by atomiser and 142 by drops. The successful sedation rate was 82.5% (95% CI 75.3-87.9%) and 84.5% (95% CI 77.7-89.5%) for atomiser and drops, respectively (p = 0.569). Sedation tended to be less successful in older children (p = 0.028, OR 0.949, 95% CI 0.916-0.983). There were no significant complications. We conclude that both modes of dexmedetomidine administration are equally effective, although increasing age of the child was associated with a decreased likelihood of successful sedation.

Intranasal dexmedetomidine following failed chloral hydrate sedation in children.

Chloral hydrate is the most commonly used sedative for paediatric diagnostic procedures in China with a success rate of around 80%. Intranasal dexmedetomidine is used for rescue sedation in our centre. This prospective investigation evaluated 213 children aged one month to 10 years who were not adequately sedated following administration of chloral hydrate. Children were randomly assigned to receive rescue intranasal dexmedetomidine at 1 µg.kg(-1) (group 1), 1.5 µg.kg(-1) (group 2) or 2 µg.kg(-1) (group 3). The sedation level was assessed every 10 min using a modified observer's assessment of alertness/sedation scale. Successful rescue sedation in groups 1, 2 and 3 were 56 (83.6%), 66 (89.2%) and 51 (96.2%), respectively. Increasing the rescue dose was associated with an increased success rate with an odds ratio of 4.12 (95% CI 1.13-14.98), p = 0.032. We conclude that intranasal dexmedetomidine is effective for sedation in children who do not respond to chloral hydrate.

A randomised comparison of two intranasal dexmedetomidine doses for premedication in children.

We compared sedation levels in children following administration of intranasal dexmedetomidine. One hundred and sixteen children aged between 1 and 8 years were enrolled in this prospective, randomised trial. Children were assigned to receive either intranasal dexmedetomidine 1 µg.kg(-1) (Group 1) or 2 µg.kg(-1) (Group 2). Thirty-one (53%) patients from Group 1 and 38 (66%) patients from Group 2 were satisfactorily sedated at the time of anaesthetic induction. Logistic regression showed a significant interaction effect (p=0.049), with the odds ratio between Group 2 over Group 1 estimated as 1.1 (95% CI 0.5-2.7) for the 1-4 year age group, and 10.5 (95% CI 1.4-80.2) for the 5-8 year age group. Both doses produced a similar level of satisfactory sedation in children aged 1-4 years, whereas 2 µg.kg(-1) resulted in a higher proportion of satisfactory sedation in children aged 5-8 years. There were no adverse haemodynamic effects. We conclude that intranasal dexmedetomidine in a premedication dose of 2 µg.kg(-1) resulted in excellent sedation in children.

Optimal timing for the administration of intranasal dexmedetomidine for premedication in children.

Previous studies have shown that 1 µg.kg(-1) intranasal dexmedetomidine produces significant sedation in children aged between 2 and 12 years. This investigation was designed to evaluate the onset time. One hundred children aged 1-12 years of ASA physical status 1-2 undergoing elective surgery were randomly allocated to five groups. Patients in groups A to D received intranasal dexmedetomidine 1 µg.kg(-1) . Patients in Group E received intranasal placebo (0.9% saline). Children from groups A, B, C, D and E had intravenous cannulation attempted at 30, 45, 60, 75 and 45 min respectively after intranasal drug or placebo administration. Vital signs, behaviour and sedation status of the children were assessed regularly until induction of anaesthesia. More children from groups A to D achieved satisfactory sedation at the time of cannulation when compared to group E (p < 0.001). The proportion of children who achieved satisfactory sedation was not significantly different among groups A to D. Overall 62% of the children who received intranasal dexmedetomidine had satisfactory sedation at the time of cannulation. The median (95% CI) time for onset of sedation was 25 (25-30) min. The median (95% CI) duration of sedation was 85 (55-100) min.

Persistent pain in patients following scoliosis surgery.

Chronic or persistent pain is increasingly recognised as a consequence of surgery in a number of different disciplines. The pain often exhibit qualities that differ from the acute post-operative pain and may represent changes in the central nervous system. There is lack of information regarding the incidence of persistent pain in patients following spinal surgery for scoliosis. This study aims to estimate the incidence of persistent pain following spinal surgery for scoliosis in a group of mainly adolescent patients. Questionnaires were distributed to consecutive patients attending the outpatient clinic of a hospital with specialist services in paediatric orthopaedics and spinal surgery. One hundred and five patients out of 122 eligible patients completed the survey. Fifty-two percent had ongoing pain upon hospital discharge either in the primary surgical site and/or in the iliac bone graft site. Approximately 10 and 7% of all patients had back and pelvic pain persisting beyond 12 months, respectively. A small proportion described elements of neuropathic pain. There was a trend suggesting that those who experienced more severe post-operative pain were more likely to develop persistent pain. These data are consistent with those reports that implicate surgery as the trigger for chronic pain.

Severe hypotension and hepatic dysfunction in a patient undergoing scoliosis surgery in the prone position.

Many patients with neuromuscular disorders develop progressive scoliosis and require corrective surgery. We present a patient with hereditary motor and sensory neuropathies who developed severe hypotension during corrective surgery for thoracolumbar scoliosis. The haemodynamic disturbance was probably secondary to thoracic hyperlordosis and the knee-chest position and was aggravated by surgical manipulation. This may be prevented by tailored preoperative evaluation of different patient prone position supports and frames in order to select that which causes least cardiovascular and respiratory disturbance. This patient also developed severely deranged liver function postoperatively and the possible aetiology is discussed.