Lesch-Nyhan disease in a 20-year-old man incorrectly described as developing 'cerebral palsy' after general anaesthesia in infancy

Lesch–Nyhan disease (LND) is a rare X-linked recessive genetic disorder caused by a deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT) enzyme. The classic clinical condition is characterized by cognitive impairment, hypotonia at rest, choreoathetosis, hyperuricaemia and the hallmark symptom of severe and involuntary self-mutilation. We describe a man with LND who was initially thought to have suffered from a dyskinetic cerebral palsy after an uncomplicated inguinal herniorrhaphy under general anaesthesia at 5 1/2 months of age. In the absence of overt self-injurious behaviour, the diagnosis was not considered for nearly two decades. The diagnosis of LND was established at 20 years of age through clinical review, biochemical examinations and molecular analysis. HPRT haemolysate activity was 7.6% of the normal control, suggesting that he had a milder variant of the disease. Mutation analysis of the HPRT gene revealed a novel missense mutation, c.449T > G in exon 6 (p.V150G). Cascade testing of family members revealed that the mother was heterozygous for the mutation but two siblings (a brother and a sister) did not carry the sequence mutation. Whether the onset of neurological abnormalities in this particular case can be attributed to the general anaesthesia is discussed.

Identifying and exploring factors influencing career choice, recruitment and retention of anaesthesia trainees in the UK

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Psychological preparation and postoperative outcomes for adults undergoing surgery under general anaesthesia

Sources of support Internal sources Manchester Centre for Health Psychology, University of Manchester, UK. An award of £2000 was received to support research assistant costs. External sources British Academy, UK. We received a small research grant of £7480 to support research assistant costs.

Clinical manifestations due to pharmacological interactions in pediatric ophthalmic surgery. Topical drugs and general anaesthesia

Introduction. The authors consider the type and the incidence of the adverse effects due to the interaction between ophthalmic drugs and general anaesthesia in pediatric ophthalmic surgery. Patients and Methods. The experience included 176 general anaesthesia in 100 children aged between 9,2 months and 11,4 years (mean age 4,9 years). Results. In the 100 patients we reported: 4 cases (2.7% general anaesthesias) of sinus tachycardia with heart rhythm varying between 170 and 180 beats per minute (3.6%); 5 cases of sinus bradycardia, varying between 60 and 70 beats per minute (3.3%); 3 cases of bronchospasm (2%); 2 cases of psychomotor agitation/disturbances in pre-convulsive state after anaesthesia (1.3%); 3 cases of arterial hypotension (60-70 mmHg) (2%); 7 cases of skin rush around neck and chest (4.6%); 1 case of prolonged apnoea (0.6%). Conclusions. The clinical manifestations, principally on the cardio-circulatory and nervous system are subjected to critical revision, to foresee the pharmacological interferences and therefore to prepare the necessary measure of medical treatment.

A randomised controlled trial comparing the effect of adjuvant intrathecal 2 mg midazolam to 20 micrograms fentanyl on postoperative pain for patients undergoing lower limb orthopaedic surgery under spinal anaesthesia.

Background: Intrathecal adjuvants are added to local anaesthetics to improve the quality of neuraxial blockade and prolong the duration of analgesia during spinal anaesthesia. Used intrathecally, fentanyl improves the quality of spinal blockade as compared to plain bupivacaine and confers a short duration of post-operative analgesia. Intrathecal midazolam as an adjuvant has been used and shown to improve the quality of spinal anaesthesia and prolong the duration of post-operative analgesia. No studies have been done comparing intrathecal fentanyl with bupivacaine and intrathecal 2 mg midazolam with bupivacaine. Objective: To compare the effect of intrathecal 2 mg midazolam to intrathecal 20 micrograms fentanyl when added to 2.6 ml of 0.5% hyperbaric bupivacaine, on post-operative pain, in patients undergoing lower limb orthopaedic surgery under spinal anaesthesia. Methods: A total of 40 patients undergoing lower limb orthopaedic surgery under spinal anaesthesia were randomized to two groups. Group 1: 2.6mls 0.5% hyperbaric bupivacaine with 0.4mls (20micrograms) fentanyl Group 2: 2.6mls of 0.5% hyperbaric bupivacaine with 0.4mls (2mg) midazolam Results: The duration of effective analgesia was longer in the midazolam group (384.05 minutes) as compared to the fentanyl group (342.6 minutes). There was no significant difference (P 0.4047). The time to onset was significantly longer in midazolam group 17.1 minutes as compared to the fentanyl group 13.2 minutes (P 0.023). The visual analogue score at rescue was significantly lower in the midazolam group (5.55) as compared to the fentanyl group 6.35 (P - 0.043). Conclusion: On the basis of the results of this study, there was no significant difference in the duration of effective analgesia between adjuvant intrathecal 2 mg midazolam as compared to intrathecal 20 micrograms fentanyl for patients undergoing lower limb orthopaedic surgery.

A randomised controlled trial comparing weight adjusted dose versus fixed dose prophylactic phenylephrine infusion on maintaining systolic blood pressure during caesarean section under spinal anaesthesia.

Background: Spinal anaesthesia is the standard of care for elective caesarean delivery. It has advantages over general anaesthesia. However the sympathetic blockade induced by spinal anaesthesia results in an 80 percent incidence of hypotension without prophylactic management. Current evidence supports co-loading with intravenous fluids in conjunction with the use of vasopressors as the most effective way to prevent and treat the hypotension. Phenylephrine is the accepted vasopressor of choice in the parturient. A prophylactic phenylephrine infusion combined with a fluid co-load is proven to be an effective and safe method of maintaining maternal hemodynamic stability. While most published studies have assessed the effectiveness of a prophylactic phenylephrine fixed dose infusion, few studies have assessed the effect of a prophylactic phenylephrine weight adjusted dose infusion on maintaining maternal hemodynamic stability following spinal anesthesia for a cesarean delivery. Objective: To compare the incidence of hypotension between women undergoing elective caesarean section under spinal anaesthesia, receiving prophylactic phenylephrine infusion at a fixed dose of 37.5 micrograms per minute versus a weight adjusted dose of 0.5 micrograms per kilogram per minute. Methods: One hundred and eight patients scheduled for non-urgent caesarean section under spinal anaesthesia were randomized into 2 groups; control group and intervention group using a computer generated table of numbers. Control group; Received prophylactic phenylephrine fixed dose infusion at 37.5 micrograms per minute. Intervention group; Received prophylactic phenylephrine weight adjusted dose infusion at 0.5 micrograms per kilogram per minute Results: The two groups had similar baseline characteristics in terms of ; Age, sex, weight and height. There was a 35.2% incidence of hypotension in the fixed dose group and an 18.6% incidence of hypotension in the weight adjusted dose group. This difference was found to be of borderline statistical significance p-value 0.05, and the difference in the incidence rates between the two groups was found to be statistically significant p= 0.03. The difference in the incidence of reactive hypertension and bradycardia between the two groups was not statistically significant: p-value of 0.19 for reactive hypertension and p-value of 0.42 for the incidence of bradycardia. There was also no statistically significant difference in the use of phenylephrine boluses, use of atropine, intravenous fluid used and the number of times the infusion was stopped. Conclusion: Among this population, the incidence of hypotension was significantly less in the weight adjusted dose group than in the fixed dose group. There was no difference in the number of physician interventions required to keep the blood pressure within 20% of baseline, and no difference in the proportion of reactive hypertension or bradycardia between the two groups. Administering prophylactic phenylephrine infusion at a weight adjusted dose of 0.5 micrograms per kilogram per minute results in a lower incidence of hypotension compared to its administration at a fixed dose of 37.5 micrograms per minute.

Orthopaedic anaesthesia for upper extremity procedures in a Nigerian hospital

Background General anaesthesia and regional anaesthesia have been used successfully for upper extremity orthopaedic procedures. Despite the advantages of regional anaesthesia, there is low utilisation in Nigeria. In this study, we assessed the types of anaesthesia employed for upper extremity surgeries in our centre. Methods After obtaining approval from the institutional ethics committee, all the patients who had upper extremity surgeries from 1 January 2011 to 31 December 2012 were included in this review. Both prospective and retrospective data were gathered. The choice of anaesthesia was at the discretion of the attending anaesthetist. Results A total of 226 patients with a male-to-female ratio of 1.6:1 and median age of 35.0 (range 2 – 89) years, had orthopaedic upper extremity procedures during the study period. Sixty-three cases (27.9%) had general anaesthesia, 5 (2.2%) combined regional and general anaesthesia while 158 (69.9%) had regional blocks. The regional blocks comprised 145 (89%) different approaches to the brachial plexus and 18 (11%) local anaesthetic infiltrations. The arm was the site mostly operated upon; while supraclavicular and axillary brachial plexus blocks were performed in equal amounts. In 14 (6.2%) patients, brachial plexus blocks were performed with spinal anaesthesia because of concomitant iliac crest bone grafts. While the duration of surgery did not differ significantly, regional anaesthesia provided a significantly longer duration of anaesthesia than general anaesthesia (251 ± 70.8 min versus 141.3 ± 65.5 min; p = 0.0000001). Conclusion There is a high use of regional anaesthesia for upper extremity orthopaedic surgeries in our centre, which is a positive development in a resource limited setting.

Pharmacokinetic Profile of Liposome-Encapsulated Ropivacaine after Maxillary Infiltration Anaesthesia

The aim of this study was to determine the pharmacokinetic parameters of liposomal ropivacaine after dental anesthesia in 14 healthy volunteers. In this randomized, double-blind and crossover study, the volunteers received maxillary infiltration of liposome-encapsulated 0.5% ropivacaine and, 0.5% ropivacaine with 1:200,000 epinephrine in two different sessions. Blood samples were collected before and after (from 15 to 1440 min) the administration of either ropivacaine formulation. HPLC with UV detection was used to quantify plasma ropivacaine concentrations. The pharmacokinetic parameters AUC(0-24) (area under the plasma concentration x time curve from baseline to 24 h), AUC(0-infinity) (area under the plasma concentration-time curve from baseline to infinity), C-max (maximum drug concentration), CL (renal clearance), T-max (maximum drug concentration time), t(1/2) (elimination half-life) and Vd (volume of distribution) were analyzed using the Wilcoxon signed-rank test. No differences (p > 0.05) were observed between both formulations for any of the pharmacokinetic parameters evaluated and plasma ropivacaine concentrations, considering each period of time. Both formulations showed similar pharmacokinetic profiles, indicating that the liposomal formulation could be a safer option for use of this local anesthetic, due to the absence of a vasoconstrictor.

The Post-Anaesthesia N-acetylcysteine Cognitive Evaluation (PANACEA) trial: study protocol for a randomised controlled trial

BACKGROUND: Some degree of cognitive decline after surgery occurs in as many as one quarter of elderly surgical patients, and this decline is associated with increased morbidity and mortality. Cognition may be affected across a range of domains, including memory, psychomotor skills, and executive function. Whilst the exact mechanisms of cognitive change after surgery are not precisely known, oxidative stress and subsequent neuroinflammation have been implicated. N-acetylcysteine (NAC) acts via multiple interrelated mechanisms to influence oxidative homeostasis, neuronal transmission, and inflammation. NAC has been shown to reduce oxidative stress and inflammation in both human and animal models. There is clinical evidence to suggest that NAC may be beneficial in preventing the cognitive decline associated with both acute physiological insults and dementia-related disorders. To date, no trials have examined perioperative NAC as a potential moderator of postoperative cognitive changes in the noncardiac surgery setting.

METHODS AND DESIGN: This is a single-centre, randomised, double-blind, placebo-controlled clinical trial, with a between-group, repeated-measures, longitudinal design. The study will recruit 370 noncardiac surgical patients at the University Hospital Geelong, aged 60 years or older. Participants are randomly assigned to receive either NAC or placebo (1:1 ratio), and groups are stratified by age and surgery type. Participants undergo a series of neuropsychological tests prior to surgery, 7 days, 3 months, and 12 months post surgery. It is hypothesised that the perioperative administration of NAC will reduce the degree of postoperative cognitive changes at early and long-term follow-up, as measured by changes on individual measures of the neurocognitive battery, when compared with placebo. Serum samples are taken on the day of surgery and on day 2 post surgery to quantitate any changes in levels of biomarkers of inflammation and oxidative stress.

DISCUSSION: The PANACEA trial aims to examine the potential efficacy of perioperative NAC to reduce the severity of postoperative cognitive dysfunction in an elderly, noncardiac surgery population. This is an entirely novel approach to the prevention of postoperative cognitive dysfunction and will have high impact and translatable outcomes if NAC is found to be beneficial.

Anaesthesia and analgesia in laboratory adult zebrafish: A question of refinement

Anaesthesia is used daily in fish experimental procedures; however, the use of an inadequate anaesthetic protocol can compromise not only the animal’s welfare but also the reliability of results. The use of zebrafish (Danio rerio) in biomedical research has increased in the last decades, highlighting the importance of appropriate anaesthetic regimens for this species. This article reviews the main anaesthetic agents and protocols used in laboratory adult zebrafish, and some of the analgesic methods to be used in this species that still need more research. In addition, a systematized observation of signs is proposed to evaluate adult zebrafish welfare to reduce pain and distress.