Changes in Tracheal Tube Cuff Pressure and Recurrent Laryngeal Nerve Conductivity During Thyroid Surgery.

BACKGROUND: The aetiology of recurrent laryngeal nerve (RLN) neurapraxia is unclear in most RLN palsies post-thyroidectomy. We hypothesised that high intralaryngeal pressures impede RLN conductivity, in turn contributing to RLN palsy. Therefore, we measured tracheal tube (TT) cuff pressure (as a surrogate for intralaryngeal pressure) and RLN conduction during ten standard manoeuvres in thyroidectomy, to assess for correlation between cuff pressure and RLN conductivity. METHODS: A prospective cohort study of thyroidectomy during 2018. For each thyroid lobe, TT cuff pressure was continuously measured via an air pressure transducer. RLN conduction (amplitude and latency) was measured using continuous neuromonitoring. Changes in mean TT cuff pressure and median nerve conduction from baseline measurements were analysed using Student's t test and Wilcoxon signed-rank test. RESULTS: In a total of 50 RLNs, the mean baseline TT cuff pressure of 19.5 ± 8.9 mmHg increased significantly to 22.0 mmHg during anteromedial rotation of the thyroid (p < 0.05). RLN conduction changed during manipulation of the superior thyroid pole with shortening of latency (-0.49% from baseline, p = 0.05) and reduction in amplitude (-12.0% from baseline, p = 0.02). The timing of these deviations did not correlate with the increased TT cuff pressure. In three cases of temporary RLN palsy, the mean cumulative case TT cuff pressure was significantly higher (24.8 mmHg, p = 0.02). CONCLUSIONS: This study demonstrates that TT cuff pressure and RLN conductivity can change significantly with manipulation of the thyroid and that high TT cuff pressures may be associated with RLN injuries.

The Foregger Midget: a machine that traveled.

Next year marks the 100th anniversary of the founding of the Foregger Company, an important manufacturer of anesthetic equipment in the first half of the 20th century. Founded by Richard von Foregger in a barn in Long Island, New York in 1914, the Foregger Company developed equipment in collaboration with anesthesiologists. Their first product was the Gwathmey machine, built around the rudimentary flowmeter designed by the anesthesiologist, James Tayloe Gwathmey. This machine was the cornerstone of future anesthetic machine development. As the company grew, von Foregger formed other liaisons, joining forces with Ralph Waters to create the Waters to-and-fro canister for carbon dioxide absorption, and with Arthur Guedel, a variety of nontraumatic airways. The combined creativity of these three men ultimately led to the Foregger Midget. This portable machine extended the reach of the Foregger Company well beyond the shores of America, as far away as the isolated west coast of Australia.

Investigation of the safety of irreversible electroporation in humans.

PURPOSE: A single-center prospective nonrandomized cohort study was performed to investigate the safety of irreversible electroporation (IRE) for tumor ablation in humans. MATERIALS AND METHODS: Thirty-eight volunteers with advanced malignancy of the liver, kidney, or lung (69 separate tumors) unresponsive to alternative treatment were subjected to IRE under general anesthesia. Clinical examination, biochemistry, and computed tomography (CT) scans of the treated organ were performed before, immediately after, and at 1 month and 3 months after the procedure. RESULTS: No mortalities occurred at 30 days. Transient ventricular arrhythmia occurred in four patients, and electrocardiographically (ECG) synchronized delivery was used subsequently in the remaining 30 patients, with two further arrhythmias (supraventricular tachycardia and atrial fibrillation). One patient developed obstruction of the upper ureter after IRE. One adrenal gland was unintentionally directly electroporated, which produced transient severe hypertension. There was no other evidence of adjacent organ damage related to the electroporation. Other adverse events were not directly related to IRE, but two patients developed temporary neurapraxia as a result of arm extension during a prolonged period of anesthesia. Although not a primary aim of this preliminary study, complete target tumor ablation verified by CT was achieved in 46 of the 69 tumors treated with IRE (66%). Most treatment failures occurred in renal and lung tumors. Biopsy in three patients showed coagulative necrosis in the regions treated by IRE. CONCLUSIONS: IRE appears to be safe for human clinical use provided ECG-synchronized delivery is used. Comparative evaluation with alternative ablative technologies is warranted.

Acute modulation of vasoconstrictor responses by pravastatin in small vessels.

BACKGROUND: Statins have been shown to inhibit conduit vessel constrictor responses via the endothelial nitric oxide (NO) pathway. Clinical studies have implicated an effect in microvascular resistance vessels; however, direct effects of therapeutically relevant statin concentrations have not been examined. We examined the effect of acute pravastatin pretreatment on vasoconstrictor responsiveness of isolated rat mesenteric small vessels. METHODS AND RESULTS: Pravastatin (112 nmol/L) pretreatment for 60 min reduced both the potency and maximal constrictor responses to phenylephrine, thromboxane (U46619) and serotonin in small vessels. This effect was abolished by endothelial denudation, NO synthase (NOS) inhibition with N-ω-nitro-L-arginine methyl ester (L-NAME 300 µmol/L) and Akt inhibition (Akt1/2 kinase inhibitor 500 nmol/L), confirming an endothelium-dependent mechanism and implicating a NO-mediated effect via the Akt pathway. Maximal superoxide scavenging with polyethylene glycol-superoxide dismutase (PEG-SOD), 150 U/ml did not influence phenylephrine constrictor responses but potentiated pravastatin's effect, suggesting that the statin did not increase NO bioavailability merely via an antioxidant mechanism. In contrast, pravastatin did not affect endothelin-1 (ET-1) constrictor responses. However, after pre-incubation with a selective endothelin-B (ET(B)) receptor antagonist (BQ788 3 µmol/L) pravastatin inhibited ET-1 constriction, suggesting that its effect is via the same mechanistic pathway as the ET(B) receptor. CONCLUSIONS: In small vessels, pravastatin inhibits constrictor responses by increasing endothelial NO bioavailability via the Akt pathway. Furthermore, ET(B) receptor blockade unmasks this effect in ET-1 constrictor responses.

A biography of Dr Carl Bodon: Pioneer of intracardiac injection of adrenaline.

This biographical essay will provide historical insights about Dr Carl Bodon who performed one of the first successful intracardiac injections of adrenaline to a patient and made important contributions to the understanding of cardiac diseases and women's health. Dr Bodon's biography reveals the story of a medical doctor who lived during tumultuous times between two world wars and ultimately died in the Holocaust. His story sheds light on forgotten contributors to the medical field and its practices.

Irreversible electroporation: a new challenge in "out of operating theater" anesthesia.

BACKGROUND: Bioelectrics, an interesting new area of medicine, combines pulsed high-voltage engineering with cell biology and has many potential applications. Pulsed electric current can be used to produce irreversible electroporation (IRE) of cell membranes with resulting cell death. This process has been shown to ablate tumors in animal studies. METHODS: A clinical trial of IRE as a tumor ablation therapy was performed at our institution. A pulsating direct current of 20 to 50 A and 500 to 3000 V was delivered into metastatic or primary tumors in the liver, kidney, or lung via needle electrodes inserted under computed tomography (CT) or ultrasound guidance. Patients required a relaxant general anesthetic. We describe some challenges presented to anesthesiologists. Guidelines for anesthesia were produced and modified as issues became apparent. The patients' charts were audited throughout. RESULTS: We noted a number of issues. The electrical discharge produced generalized upper body muscular contractions requiring neuromuscular blockade. Two patients developed positional neuropraxia because of the extended arm position requested for CT scanning. After experimentation, we have developed a modified arm position. Some patients developed self-limiting ventricular tachycardias that are now minimized by using an electrocardiogram synchronizer. Three patients developed pneumothoraces as a result of the needle electrode insertion. CONCLUSIONS: Relaxant general anesthesia is required for IRE of the liver, lung, and kidney. An electrocardiogram synchronizer should be used to minimize the risk of arrhythmias. Attention to the position of the arms is required to maximize CT scan quality but minimize brachial plexus strain. Simple postoperative analgesia is all that is required in most patients.

From cholera to COVID-19: How pandemics have shaped the development of anaesthesia and intensive care medicine.

The infectious pandemics and epidemics of the past 200 years have caused millions of deaths. However, these devastating events have also led to creative thinking, imaginative experimentation and the evolution of medical care. As a result, the history of critical care medicine is entwined with the story of these global disasters. This article will take case studies from recent pandemics and epidemics and examine their impact on the development of anaesthesia and intensive care medicine.

'Neither a borrower nor a lender be': Letters from the anaesthetist Joseph Thomas Clover to the Birmingham surgeon Joseph Sampson Gamgee.

The London surgeon and anaesthetist, Joseph Thomas Clover (1825-1882), and the Birmingham surgeon, Joseph Sampson Gamgee (1828-1886), are well known figures in the history of medicine. Draft letters among the surviving papers of Joseph Clover have been transcribed and reveal new information about their friendship, their financial affairs and Clover's motivation to become a full-time anaesthetist. They have also led to the discovery that Gamgee was briefly imprisoned in Warwick County Goal for debt in 1859.

Improving outcomes in non-small cell lung cancer; population analysis of radical radiotherapy.

AIM: Regional utilisation of radical radiotherapy (RT) in non-small cell lung cancer (NSCLC) was used to define optimal utilisation to improve outcome and as a surrogate for evidence of RT efficacy. PATIENTS & METHODS: 65,412 NSCLC cases diagnosed in England 2012-13 were linked to comprehensive national radiotherapy dataset, hospital admissions and the Office of National Statistics. Geographical variation in utilisation was determined using a multivariate binary logistic regression analysis after adjusting for age, stage, deprivation, comorbidity and other radical treatment and the effect of radical RT utilisation on survival was investigated. Survival was adjusted for dependent and independent variables and the effect of differing levels of utilisation was assessed by the log likelihood test. RESULTS: 17.6% cases potentially eligible for radical RT (stages 0-III) received radiotherapy with radical intent. Utilisation of radical RT had an impact on survival (p < 0.00001). Adjusting for all prognostic and treatment variables counties with lowest utilisation (≤15%) had the worst survival (HR = 1.13). The highest utilisation quintile counties (≥25%) had worse survival compared to counties with lower utilisation (≈20%) (p < 0.0001). Analysis of stages II&III showed the same pattern; increase in utilisation from 20% to ≥25% resulting in a 3% drop in 2-year population survival (p = 0.001). CONCLUSION: The utilisation of radical RT has a significant impact on NSCLC population survival. Improvement in survival of NSCLC population can be achieved by offering radical RT to a larger proportion of patients while avoiding excessive use. Geographical variation in RT utilisation provides indirect evidence of survival benefit of radical radiotherapy.

A novel bioassay for B-cell activating factor (BAFF) based on expression of a BAFF-receptor ectodomain-tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor-2 endodomain fusion receptor in human rhabdomyosarcoma cells.

B-cell activating factor (BAFF) is a type II transmembrane glycoprotein belonging to the tumour necrosis factor ligand superfamily. Active soluble forms of BAFF are generated either by cleavage of the extracellular domain or by recombinant DNA technology. The current bioassay for measuring the activity of soluble BAFF involves stimulation of the proliferation of mouse splenic B-cells in the presence of goat anti-mouse IgMmicro chain which is rather cumbersome and lengthy and yields variable results. We have therefore developed an alternative functional assay which relies on the ability of BAFF to induce an apoptotic response in human rhabdomyosarcoma cells. For this, we constructed a chimeric receptor containing the ectodomain of the MuBAFF-R--the major cell receptor for BAFF--and the endodomain of the HuTRAIL-R2--one of the two functional receptors for TRAIL--which is known to contain a death domain and trigger apoptosis. When the chimeric receptor was expressed in the TRAIL-sensitive human rhabdomyosarcoma cell line KD4 clone 21, recombinant BAFF of either human or mouse sequence stimulated apoptosis, similar to TRAIL, in a dose-dependent manner. The transfected cell population, called FL17, expressing the MuBAFF-R/ HuTRAIL-R2 thus provided the basis of a novel functional bioassay for BAFF that is simple and relatively fast to perform. The construction of the chimeric receptor, development of the transfected cells expressing this receptor and the development of sensitive and reproducible bioassays for BAFF and anti-BAFF neutralising antibodies are described.