Incidence of severe critical events in paediatric anaesthesia in the United Kingdom: secondary analysis of the anaesthesia practice in children observational trial (APRICOT study).

The anaesthesia practice in children observational trial of 31,127 patients in 261 European hospitals revealed a high (5.2%) incidence of severe critical events in the peri-operative period and wide variability in practice. A sub-analysis of the UK data was undertaken to investigate differences compared with the non-UK cohort in the incidence and nature of peri-operative severe critical events and to attempt to identify areas for quality improvement. In the UK cohort of 7040 paediatric patients from 43 hospitals, the overall incidence of peri-operative severe critical events was lower than in the non-UK cohort (3.3%, 95%CI: 2.9-3.8 vs. 5.8%, 95%CI: 5.5-6.1, RR 0.57, p < 0.001). There was a lower rate of bronchospasm (RR 0.22, 95%CI: 0.14-0.33; p < 0.001), stridor (RR 0.42, 95%CI: 0.28-0.65; p < 0.001) and cardiovascular instability (RR 0.69, 95%CI: 0.55-0.86; p = 0.001) than in the non-UK cohort. The proportion of sicker patients where less experienced teams were managing care was lower in the UK than in the non-UK cohort (10.4% vs. 20.4% of the ASA physical status 3 and 9% vs. 12.9% of the ASA physical status 4 patients). Differences in work-load between centres did not affect the incidence and outcomes of severe critical events when stratified for age and ASA physical status. The lower incidence of cardiovascular and respiratory complications could be partly attributed to more experienced dedicated paediatric anaesthesia providers managing the higher risk patients in the UK. Areas for quality improvement include: standardisation of serious critical event definitions; increased reporting; development of evidence-based protocols for management of serious critical events; development and rational use of paediatric peri-operative risk assessment scores; implementation of current best practice in provision of competent paediatric anaesthesia services in Europe; development of specific training in the management of severe peri-operative critical events; and implementation of systems for ensuring maintenance of skills.

Differences in Blood Pressure in Infants After General Anesthesia Compared to Awake Regional Anesthesia (GAS Study-A Prospective Randomized Trial).

BACKGROUND: The General Anesthesia compared to Spinal anesthesia (GAS) study is a prospective randomized, controlled, multisite, trial designed to assess the influence of general anesthesia (GA) on neurodevelopment at 5 years of age. A secondary aim obtained from the blood pressure data of the GAS trial is to compare rates of intraoperative hypotension after anesthesia and to identify risk factors for intraoperative hypotension. METHODS: A total of 722 infants ≤60 weeks postmenstrual age undergoing inguinal herniorrhaphy were randomized to either bupivacaine regional anesthesia (RA) or sevoflurane GA. Exclusion criteria included risk factors for adverse neurodevelopmental outcome and infants born at <26 weeks of gestation. Moderate hypotension was defined as mean arterial pressure measurement of <35 mm Hg. Any hypotension was defined as mean arterial pressure of <45 mm Hg. Epochs were defined as 5-minute measurement periods. The primary outcome was any measured hypotension <35 mm Hg from start of anesthesia to leaving the operating room. This analysis is reported primarily as intention to treat (ITT) and secondarily as per protocol. RESULTS: The relative risk of GA compared with RA predicting any measured hypotension of <35 mm Hg from the start of anesthesia to leaving the operating room was 2.8 (confidence interval [CI], 2.0-4.1; P < .001) by ITT analysis and 4.5 (CI, 2.7-7.4, P < .001) as per protocol analysis. In the GA group, 87% and 49%, and in the RA group, 41% and 16%, exhibited any or moderate hypotension by ITT, respectively. In multivariable modeling, group assignment (GA versus RA), weight at the time of surgery, and minimal intraoperative temperature were risk factors for hypotension. Interventions for hypotension occurred more commonly in the GA group compared with the RA group (relative risk, 2.8, 95% CI, 1.7-4.4 by ITT). CONCLUSIONS: RA reduces the incidence of hypotension and the chance of intervention to treat it compared with sevoflurane anesthesia in young infants undergoing inguinal hernia repair.

High-performance liquid chromatography determination of alpha1-acid glycoprotein in small volumes of plasma from neonates.

In order to investigate how the alpha1-acid glycoprotein (AGP) concentrations of neonates change in response to surgical stress, a simple high-performance liquid chromatography (HPLC)-assay for the measurement of alpha1-acid glycoprotein levels was developed. A fraction containing alpha1-acid glycoprotein was isolated from the bulk of plasma protein by addition of 0.6M perchloric acid and was then analysed directly on a short PLRP-S 4000A reversed phase column column. The method was validated by analysis of pooled plasma from healthy adults both in comparison with a calibration curve and by standard additions. The procedure was able to isolate alpha1-acid glycoprotein rapidly (<30 min) and required only 50 microl of plasma. The mean extraction recovery was 79.1% (CV 6.4%). The within-run precision for the analysis of three replicates of quality control sample ranged from +/-1.2 to +/-3.8% and the between-run precision was +/-6.1%. The method was linear (r(2)=0.988) over a concentration range from 6 to 100.0 mg/100 ml. The AGP levels in neonatal samples ranged from 25 to 93 mg/100 ml.

A simple microanalytical technique for the determination of paracetamol and its main metabolites in blood spots.

The use of blood spot collection cards is a simple way to obtain specimens for analysis of drugs with a narrow therapeutic window. We describe the development and validation of a microanalytical technique for the determination of paracetamol and its glucuronide and sulphate metabolites from blood spots. The method is based on reversed phase high-performance liquid chromatography with ultraviolet detection. The limit of detection of the method is 600 pg on column for paracetamol. Intra- and inter-day precision of the determination of paracetamol was 7.1 and 3.2% respectively. The small volume of blood required (20 microl), combined with the simplicity of the analytical technique makes this a useful procedure for monitoring paracetamol concentrations. The method was applied to the analysis of blood spots taken from neonates being treated with paracetamol.

Analysis of unconjugated morphine, codeine, normorphine and morphine as glucuronides in small volumes of plasma from children.

A sensitive method for the analysis of unconjugated morphine, codeine, normorphine and total morphine after hydrolysis of glucuronide conjugates is described. The method was applicable to 50-microliters volumes of plasma. The analytes were converted to heptafluorobutyryl (HFB) derivatives before analysis by gas chromatography-negative ion chemical ionization mass spectrometry. Morphine and codeine were quantified against their [2H3]-isotopomers. Linearity, precision and accuracy were quite acceptable (in the 10(-10)-10(-9) g range), and the absolute limits of detection were < 1 pg.

Amethocaine gel for percutaneous local anaesthesia.

Amethocaine gel is a recently developed formulation of amethocaine, designed to provide percutaneous local anaesthesia. Its pharmacological characteristics coupled with a phase-change gel formulation may confer therapeutic advantages over existing preparations. Percutaneous local anaesthesia has increasing relevance in analgesia for paediatric procedures and superficial surgical operations.

Pulmonary surfactant: physiology, pharmacology and clinical uses.

The endogenous surfactant system in the lungs is complex. The synthetic, recycling and metabolic pathways are clear but the controlling mechanisms are not fully understood. Surfactant-specific proteins are important and their isolation and manufacture opens up new prospects for production of a synthetic surfactant with all the properties of natural human surfactant for therapy and prophylaxis of neonatal respiratory distress syndrome.

Prolonged neuromuscular blockade with vecuronium in a neonate with renal failure.

An 11-day-old neonate with renal failure caused by dysplastic kidneys was anaesthetised with thiopentone, vecuronium, nitrous oxide and oxygen, for insertion of a long-term peritoneal dialysis catheter. Complete neuromuscular block of 210 minutes' duration ensued after the initial dose of vecuronium (97 micrograms/kg). Partial block persisted for a further 30 minutes. The prolonged neuromuscular block in this case may have been because of proportionately greater dependence on renal clearance of vecuronium in neonates.

Alfentanil in an anaesthetic technique for penetrating eye injuries.

Alfentanil in three doses (10, 20 and 30 micrograms/kg) was added to an anaesthetic technique suitable for penetrating eye injuries. All three doses proved effective in abolishing the marked present response to tracheal intubation which occurs with this technique, but at least 20 micrograms/kg was needed to obtund the heart rate response significantly and to facilitate early intubation. Transient hypotension and bradycardia occurred in some patients who received the highest dose of alfentanil. The incidence of postoperative sequelae was small in all groups. Thus, the optimal dose of alfentanil in an anaesthetic technique for penetrating eye injuries appears to be 20 micrograms/kg.

A survey of interhospital transport of the critically ill child in the United Kingdom.

Nineteen paediatric intensive care units were surveyed by questionnaire to provide information on the number of interhospital transfers, the experience of personal accompanying the critically ill child and the equipment available to maintain intensive care during transfer. Replies were received from 17 units. An estimated 800 transfers are performed annually. Three units routinely send intensive care staff to collect patients with an estimated 60% of transfers performed by a variety of staff from referring hospitals. Most respondents believed that existing arrangements for transfer were unsatisfactory, but only four units said that transfer may be prevented or delayed by lack of facilities. We believe that any plan to centralize paediatric intensive care in the UK should also include the means by which to transfer the patient without increasing the risk to the patient.

Stridor in an adult. An unusual presentation of functional origin.

A 34-year-old woman with a recent history of a influenza-like illness and signs of bronchopneumonia presented with many of the features of acute epiglottitis, a condition which still carries a high mortality in adults. Urgent laryngoscopy and bronchoscopy under inhalational anaesthesia were negative. The results of arterial blood gases, taken when stridor was at its worst, revealed marked hypocapnia and respiratory alkalosis. We conclude that the resultant acute reduction of serum ionised calcium produced stridor as a result of tetany of the vocal cords. Similar cases from the literature and the role of emotional factors in the aetiology are discussed.

Use of the oesophageal detector device in children under one year of age.

The efficacy of a modified oesophageal detector device was evaluated in a single-blind study of 20 healthy infants. It was found to be unreliable as a method to discriminate oesophageal from tracheal intubation in this age group.

Development of a selection and monitoring protocol for safe sedation of children.

A protocol was developed for children undergoing diagnostic and therapeutic procedures under sedation to try to raise the standards of patient selection, preparation, monitoring and management to those of children undergoing general anaesthesia. The principles underlying the protocol design were that informed consent should be obtained; fasting guidelines as for general anaesthesia should be implemented; contraindications to sedation should be actively sought; monitoring should be commenced from the time of administration of sedation until recovery and should be maintained during patient transport; personnel trained in monitoring and resuscitation of children should have as their sole duty the monitoring of the sedated child and should not take part in the procedure; the minimum monitoring standard should comprise regular assessments of the level of sedation, oxygen saturation by pulse oximetry, respiratory rate and pulse rate supplemented by temperature, ECG and blood pressure for infants, for prolonged procedures or where verbal contact with the child is lost.

Paracetamol-induced fulminant hepatic failure in a child after 5 days of therapeutic doses.

We report the case of a two and a half year-old girl who developed fulminant hepatic failure following 5 days of regular oral ingestion of paracetamol, approximately 90 mg x kg-1 x day-1. She presented with the typical findings of hepatomegaly, encephalopathy, high ammonia levels, high transaminases, hypoglycaemia and lactic acidosis. After stabilization, she was transferred to a specialist paediatric liver failure unit and fortunately she made a full recovery with intensive medical management.

Analgesic efficacy of paracetamol and diclofenac in children receiving PCA morphine.

We studied 80 children, aged 5-13 yr, who received PCA with morphine after appendicectomy using a standardized tracheal general anaesthetic. All patients received morphine 0.1 mg kg-1 before surgical incision and all had wound infiltration with bupivacaine 1 mg kg-1 at the end of surgery. Patients were allocated randomly to receive postoperative analgesia with PCA morphine alone, morphine plus diclofenac 1 mg kg-1, morphine plus paracetamol 15-20 mg kg-1 or morphine plus a combination of both diclofenac and paracetamol. Cumulative morphine consumption was significantly reduced by concurrent administration of diclofenac but no additive effect of paracetamol was demonstrable with the doses used in the study. Analgesia, as assessed by movement pain scoring, was significantly improved by the addition of diclofenac despite lower morphine consumption. Adverse effects and duration of PCA were comparable in the four groups.