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1.
BJA Educ ; 24(3): 84-90, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38375493
2.
BJA Educ ; 23(9): 350-357, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37600215
3.
Transplant Proc ; 53(7): 2382-2389, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34412912

ABSTRACT

BACKGROUND: Combined multivisceral transplantation has emerged as a therapeutic option for a select patient cohort; however, clinical decision-making remains complex and controversial. The aim of this study was to examine patient characteristics, operative complications, and long-term outcomes of all patients who have undergone combined heart-lung-liver transplantation (HLLTx) in Australia. METHODS: In this study, we performed a retrospective analysis of all adult patients who have undergone combined HLLTx in Australia to date. Recipient clinical characteristics, waitlist, and transplant outcomes are described. RESULTS: Eight adult patients have received HLLTx at a single Australian transplant center. Recipients of HLLTx have typically been young (median age, 30.1 years; range, 24-37), underweight (median body mass index, 19.8 kg/m2; range, 16.2-30.4) patients with cystic fibrosis (n = 8, 100%) with severe airflow obstruction (median forced expiratory volume in the first second of expiration, 24% predicted; range, 17%-48%) accompanied by liver cirrhosis confirmed on histopathology (n = 8, 100%). Despite relative preservation of synthetic function and low model for end-stage liver disease scores (median, 8; range, 6-17), all recipients had complications of portal hypertension prior to transplantation, with many patients having suffered life-threatening variceal hemorrhage. In this cohort, HLLTx was associated with overall posttransplant survival of 87.5% at 30 days, 71.4% at 1 year, and 42.9% at 5 years. Listing for combined HLLTx was associated with prolonged waitlist times relative to bilateral sequential single-lung transplantation (median 556 vs 56 days, respectively), however waitlist mortality and/or delisting was comparable between groups. CONCLUSIONS: Taken together, these findings highlight the opportunities and challenges facing combined (heart-) lung and liver transplantation in patients with multiorgan failure.


Subject(s)
Cystic Fibrosis , End Stage Liver Disease , Esophageal and Gastric Varices , Liver Transplantation , Lung Transplantation , Adult , Australia , Cystic Fibrosis/surgery , Gastrointestinal Hemorrhage , Humans , Lung , Lung Transplantation/adverse effects , Retrospective Studies , Severity of Illness Index
5.
Anaesthesia ; 76(5): 655-664, 2021 05.
Article in English | MEDLINE | ID: mdl-33399225

ABSTRACT

Malignant hyperthermia is defined in the International Classification of Diseases as a progressive life-threatening hyperthermic reaction occurring during general anaesthesia. Malignant hyperthermia has an underlying genetic basis, and genetically susceptible individuals are at risk of developing malignant hyperthermia if they are exposed to any of the potent inhalational anaesthetics or suxamethonium. It can also be described as a malignant hypermetabolic syndrome. There are no specific clinical features of malignant hyperthermia and the condition may prove fatal unless it is recognised in its early stages and treatment is promptly and aggressively implemented. The Association of Anaesthetists has previously produced crisis management guidelines intended to be displayed in all anaesthetic rooms as an aide memoire should a malignant hyperthermia reaction occur. The last iteration was produced in 2011 and since then there have been some developments requiring an update. In these guidelines we will provide background information that has been used in updating the crisis management recommendations but will also provide more detailed guidance on the clinical diagnosis of malignant hyperthermia. The scope of these guidelines is extended to include practical guidance for anaesthetists dealing with a case of suspected malignant hyperthermia once the acute reaction has been reversed. This includes information on care and monitoring during and after the event; appropriate equipment and resuscitative measures within the operating theatre and ICU; the importance of communication and teamwork; guidance on counselling of the patient and their family; and how to make a referral of the patient for confirmation of the diagnosis. We also review which patients presenting for surgery may be at increased risk of developing malignant hyperthermia under anaesthesia and what precautions should be taken during the peri-operative management of the patients.


Subject(s)
Dantrolene/therapeutic use , Malignant Hyperthermia/drug therapy , Muscle Relaxants, Central/therapeutic use , Acidosis/drug therapy , Acidosis/etiology , Body Temperature , Calcium/administration & dosage , Carbon Dioxide/analysis , Compartment Syndromes/drug therapy , Compartment Syndromes/etiology , Disseminated Intravascular Coagulation/etiology , Disseminated Intravascular Coagulation/therapy , Heart Rate , Humans , Hyperkalemia/drug therapy , Hyperkalemia/etiology , Malignant Hyperthermia/complications , Malignant Hyperthermia/diagnosis , Myoglobinuria/drug therapy , Myoglobinuria/etiology , Pulmonary Ventilation , Risk Factors , Sodium Bicarbonate/administration & dosage
10.
Br J Anaesth ; 123(1): e29-e37, 2019 Jul.
Article in English | MEDLINE | ID: mdl-31029409

ABSTRACT

BACKGROUND: Grading schemes for severity of suspected allergic reactions have been applied to the perioperative setting, but there is no scoring system that estimates the likelihood that the reaction is an immediate hypersensitivity reaction. Such a score would be useful in evaluating current and proposed tests for the diagnosis of suspected perioperative immediate hypersensitivity reactions and culprit agents. METHODS: We conducted a Delphi consensus process involving a panel of 25 international multidisciplinary experts in suspected perioperative allergy. Items were ranked according to appropriateness (on a scale of 1-9) and consensus, which informed development of a clinical scoring system. The scoring system was assessed by comparing scores generated for a series of clinical scenarios against ratings of panel members. Supplementary scores for mast cell tryptase were generated. RESULTS: Two rounds of the Delphi process achieved stopping criteria for all statements. From an initial 60 statements, 43 were rated appropriate (median score 7 or more) and met agreement criteria (disagreement index <0.5); these were used in the clinical scoring system. The rating of clinical scenarios supported the validity of the scoring system. Although there was variability in the interpretation of changes in mast cell tryptase by the panel, we were able to include supplementary scores for mast cell tryptase. CONCLUSION: We used a robust consensus development process to devise a clinical scoring system for suspected perioperative immediate hypersensitivity reactions. This will enable objectivity and uniformity in the assessment of the sensitivity of diagnostic tests.


Subject(s)
Hypersensitivity, Immediate/diagnosis , Intraoperative Complications/diagnosis , Postoperative Complications/diagnosis , Consensus , Humans
11.
Br J Anaesth ; 123(1): e110-e116, 2019 Jul.
Article in English | MEDLINE | ID: mdl-30915983

ABSTRACT

BACKGROUND: Around 10-15% of the in-patient population carry unsubstantiated 'penicillin allergy' labels, the majority incorrect when tested. These labels are associated with harm from use of broad-spectrum non-penicillin antibiotics. Current testing guidelines incorporate both skin and challenge tests; this is prohibitively expensive and time-consuming to deliver on a large scale. We aimed to establish the feasibility of a rapid access de-labelling pathway for surgical patients, using direct oral challenge. METHODS: 'Penicillin allergic' patients, recruited from a surgical pre-assessment clinic, were risk-stratified using a screening questionnaire. Patients at low risk of true, immunoglobulin E (IgE)-mediated allergy were offered direct oral challenge using incremental amoxicillin to a total dose of 500 mg. A 3-day course was completed at home. De-labelled patients were followed up to determine antibiotic use in surgery, and attitudes towards de-labelling were explored. RESULTS: Of 219 patients screened, 74 were eligible for inclusion and offered testing. We subsequently tested 56 patients; 55 were de-labelled. None had a serious reaction to the supervised challenge, or thereafter. On follow-up, 17 of 19 patients received appropriate antimicrobial prophylaxis during surgery. Only three of 33 de-labelled patients would have been happy for the label to be removed without prior specialist testing. CONCLUSION: Rapid access de-labelling, using direct oral challenge in appropriately risk-stratified patients, can be incorporated into the existing surgical care pathway. This provides immediate and potential long-term benefit for patients. Interest in testing is high among patients, and clinicians appear to follow clinic recommendations. Patients are unlikely to accept removal of their allergy label on the basis of history alone. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: AN17/92982.


Subject(s)
Amoxicillin/administration & dosage , Anti-Bacterial Agents/administration & dosage , Drug Hypersensitivity/diagnosis , Elective Surgical Procedures , Penicillins/administration & dosage , Preoperative Care/methods , Feasibility Studies , Humans , United Kingdom
12.
Br J Anaesth ; 123(1): e82-e94, 2019 Jul.
Article in English | MEDLINE | ID: mdl-30916014

ABSTRACT

Unsubstantiated penicillin-allergy labels are common in surgical patients, and can lead to significant harm through avoidance of best first-line prophylaxis of surgical site infections and increased infection with resistant bacterial strains. Up to 98% of penicillin-allergy labels are incorrect when tested. Because of the scarcity of trained allergists in all healthcare systems, only a minority of surgical patients have the opportunity to undergo testing and de-labelling before surgery. Testing pathways can be modified and shortened in selected patients. A variety of healthcare professionals can, with appropriate training and in collaboration with allergists, provide testing for selected patients. We review how patients might be assessed, the appropriate testing strategies that can be used, and the minimum standards of safe testing.


Subject(s)
Anesthesia/methods , Anti-Bacterial Agents/adverse effects , Drug Hypersensitivity/diagnosis , Penicillins/adverse effects , Humans
14.
Br J Anaesth ; 121(4): 694-697, 2018 10.
Article in English | MEDLINE | ID: mdl-30236229
15.
Br J Anaesth ; 121(4): 944-952, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30236257

ABSTRACT

BACKGROUND: Gaps in our understanding of genetic susceptibility to malignant hyperthermia (MH) limit the application and interpretation of genetic diagnosis of the condition. Our aim was to define the prevalence and role of variants in the three genes implicated in MH susceptibility in the largest comprehensively phenotyped MH cohort worldwide. METHODS: We initially included one individual from each positive family tested in the UK MH Unit since 1971 to detect variants in RYR1, CACNA1S, or STAC3. Screening for genetic variants has been ongoing since 1991 and has involved a range of techniques, most recently next generation sequencing. We assessed the pathogenicity of variants using standard guidelines, including family segregation studies. The prevalence of recurrent variants of unknown significance was compared with the prevalence reported in a large database of sequence variants in low-risk populations. RESULTS: We have confirmed MH susceptibility in 795 independent families, for 722 of which we have a DNA sample. Potentially pathogenic variants were found in 555 families, with 25 RYR1 and one CACNA1S variants previously unclassified recurrent variants significantly over-represented (P<1×10-7) in our cohort compared with the Exome Aggregation Consortium database. There was genotype-phenotype discordance in 86 of 328 families suitable for segregation analysis. We estimate non-RYR1/CACNA1S/STAC3 susceptibility occurs in 14-23% of MH families. CONCLUSIONS: Our data provide current estimates of the role of variants in RYR1, CACNA1S, and STAC3 in susceptibility to MH in a predominantly white European population.


Subject(s)
Malignant Hyperthermia/epidemiology , Malignant Hyperthermia/genetics , Adaptor Proteins, Signal Transducing/genetics , Calcium Channels/genetics , Calcium Channels, L-Type , Cohort Studies , Computer Simulation , Exome , Family , Genetic Predisposition to Disease , Genetic Testing , Genetic Variation , Humans , Ryanodine Receptor Calcium Release Channel/genetics , United Kingdom/epidemiology
16.
Br J Anaesth ; 121(4): 953-961, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30236258

ABSTRACT

BACKGROUND: The human p.G2434R variant of the RYR1 gene is most frequently associated with malignant hyperthermia (MH) in the UK. We report the phenotype of a knock-in mouse that expresses the RYR1 variant p.G2435R, which is isogenetic with the human variant. METHODS: We observed the general phenotype; determined the sensitivity of myotubes to caffeine-, KCl, and halothane-induced Ca2+ release; determined the in vivo response to halothane or increased ambient temperature; and determined the in vivo myoplasmic intracellular Ca2+ concentration in skeletal muscle before and during exposure to volatile anaesthetics. RESULTS: RYR1 pG2435R/MH normal (MHS-Heterozygous[Het]) or RYR1 pG2435R/pG2435R (MHS-Homozygous[Hom]) mice were fully viable under typical rearing conditions, although some male MHS-Hom mice died spontaneously. The normalised half-maximal effective concentration (95% confidence interval) for intracellular Ca2+ release in myotubes in response to KCl [MH normal, MHN, 21.4 (19.8-23.1) mM; MHS-Het 16.2 (15.2-17.2) mM; MHS-Hom 11.2 (10.2-12.2) mM] and caffeine (MHN, 5.7 (5-6.3) mM; MHS-Het 4.5 (3.9-5.0) mM; MHS-Hom 1.77 (1.5-2.1) mM] exhibited a gene dose-dependent decrease, and there was a gene dose-dependent increase in halothane sensitivity. Intact animals show a gene dose-dependent susceptibility to MH with volatile anaesthetics or to heat stroke. RYR1 p.G2435R mice had elevated skeletal muscle intracellular resting [Ca2+]i, (values are expressed as mean (SD)) (MHN 123 (3) nM; MHS-Het 156 (16) nM; MHS-Hom 265 (32) nM; P<0.001) and [Na+]i (MHN 8 (0.1) mM; MHS-Het 10 (1) mM; MHS-Hom 14 (0.7) mM; P<0.001) that was further increased by exposure to volatile anaesthetics. CONCLUSIONS: RYR1 pG2435R mice demonstrated gene dose-dependent in vitro and in vivo responses to pharmacological and environmental stressors that parallel those seen in patients with the human RYR1 variant p.G2434R.


Subject(s)
Calcium/metabolism , Heat Stress Disorders/genetics , Malignant Hyperthermia/genetics , Ryanodine Receptor Calcium Release Channel/genetics , Anesthetics, Inhalation/pharmacology , Animals , Caffeine/pharmacology , Calcium Signaling/drug effects , Calcium Signaling/genetics , Dose-Response Relationship, Drug , Gene Knock-In Techniques , Halothane/pharmacology , Male , Mice , Mice, Inbred C57BL , Muscle Fibers, Skeletal/drug effects , Muscle, Skeletal/drug effects , Muscle, Skeletal/metabolism , Mutation/genetics , Phenotype , Potassium Chloride/pharmacology
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