John W Sear

John W Sear
University of Oxford | OX · Nuffield Department of Clinical Neurosciences

MA BSc MBBS PhD FFARCS FANZCA

About

321
Publications
66,877
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7,837
Citations
Citations since 2017
7 Research Items
1172 Citations
2017201820192020202120222023050100150200250
2017201820192020202120222023050100150200250
2017201820192020202120222023050100150200250
2017201820192020202120222023050100150200250

Publications

Publications (321)
Article
Background: The association between preinduction blood pressure (BP) and postoperative outcomes after noncardiac surgery is poorly understood. Whether this association depends on the presence of risk factors for poor cardiovascular outcomes remains unclear. Accordingly, we evaluated the association between preinduction BP and its different compone...
Article
Purpose of review: The current review examines the success and failures of the development of new hypnotic compounds for the human market. One of the important aspects is that one of the key present agents, propofol, is considered by many anaesthesiologists as 'the ideal'. However, all drugs have adverse or side-effects. Recent findings: The las...
Chapter
Among the first reports of the intravenous injection of drugs are those describing the studies of Wren and Major (Philos Trans R Soc Lond 1:128–30, 1665; Cirurgia infusoria placidis CL: vivorium dubiis impugnata, cun modesta, ad eadem. Responsione. Kiloni, 1667). They injected opium dissolved in water into the venous system of a dog, which caused i...
Chapter
The first of the modern generation of intravenous agents for the induction (and maintenance) of anesthesia dates back to the introduction and evaluation of thiopental in 1934 (Lundy and others). Since then, there have been a large number of intravenous agents introduced and in parallel a number which have undergone clinical usage and then withdrawn...
Article
Full-text available
Objectives: The aim of the study was to assess simultaneous pharmacokinetics and thermal and mechanical antinociception after intramuscular methadone (0.6 mg/kg) in 10 cats. Methods: Thermal and mechanical threshold (TT and MT, respectively) testing and blood collection were conducted at baseline and up to 24 h after administration. Methadone pl...
Article
To evaluate the potential benefits of high-dose buprenorphine formulations for analgesia in cats, serial and crossover studies were undertaken to investigate their pharmacokinetics and thermal antinociceptive effects. Twelve healthy adult domestic shorthair cats (6.0 ± 1.1 kg bodyweight) were studied. Aqueous solutions of buprenorphine hydrochlorid...
Article
Serious post-operative neurological complications of unknown aetiology are reported in tigers after immobilization using tiletamine and zolazepam. These complications may arise from the persistent effects of tiletamine or active metabolites of tiletamine or zolazepam. Concentrations of tiletamine, zolazepam and some metabolites were measured using...
Article
Full-text available
Atenolol has been proposed as a peri-operative cardioprotective agent in patients with coronary disease. However, recent reports have cast doubt over the cardioprotective efficacy of atenolol in patients with hypertension and coronary artery disease. There is therefore doubt whether atenolol is the correct cardioprotective drug in the surgical sett...
Article
The number of percutaneous coronary interventions (PCI) performed annually has increased rapidly over the last two decades. Coronary angioplasties are now commonly complemented with the insertion of coronary artery stents. Initially bare metal stents (BMS) were developed with drug-eluting stents (DES) subsequently being introduced. Drug-eluting ste...
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Diabetes mellitus (DM) is the most common non-communicable disease worldwide. Presently there are about 150 million diabetics; it affects between 1 and 2% of the population in the United Kingdom (UK), and about 10% of the population in the United States of America (USA). There may also be an equal number of undiagnosed patients. Diabetes affects ab...
Article
ambulatory surgery. Eighty-one percent of the patients had been taking at least 1 medication (prescribed drug; over the counter medication; vitamins or minerals; herbals or natural substances) in the week before anesthesia and surgery, and 50% had been taking at least 1 “prescription drug.” Further scrutiny shows that 7% of the patients were taking...
Article
Objective Describe the pharmacokinetics of buprenorphine and norbuprenorphine in horses and to relate the plasma buprenorphine concentration to the pharmacodynamic effects.Study designSingle phase non-blinded study.AnimalsSix dedicated research horses, aged 3–10 years and weighing 480–515 kg.Methods Thermal and mechanical nociceptive thresholds, he...
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Background This post hoc analysis aimed to determine whether neuraxial block was associated with a composite of cardiovascular death, non-fatal myocardial infarction (MI) and non-fatal cardiac arrest within 30 days of randomization in POISE trial patients.MethodsA total of 8351 non-cardiac surgical patients at high risk of cardiovascular complicati...
Article
Background: In this post hoc subanalysis of the Perioperative Ischemic Evaluation (POISE) trial, we sought to determine whether nitrous oxide was associated with the primary composite outcome of cardiovascular death, nonfatal myocardial infarction (MI), and nonfatal cardiac arrest within 30 days of randomization. Methods: The POISE trial of peri...
Article
Objective To describe simultaneous pharmacokinetics (PK) and thermal antinociception after intravenous (IV), intramuscular (IM) and subcutaneous (SC) buprenorphine in cats. Study design Randomized, prospective, blinded, three period crossover experiment. Animals Six healthy adult cats weighing 4.1 ± 0.5 kg. Methods Buprenorphine (0.02 mg kg−1) was...
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Full-text available
/st> The present study examines the molecular basis of the disposition kinetics for i.v. hypnotic agents using comparative molecular field analysis (CoMFA). /st> The systemic clearance (Cl(s) litre min(-1)) and apparent volume of distribution at steady state (Vd(ss) litres) for 14 i.v. anaesthetics in human subjects were obtained from the literatur...
Article
de Vries, A., Taylor, P. M., Troughton, G., Liu, B., Fowden, A. L., Sear, J. W. Real time monitoring of propofol blood concentration in ponies anaesthetized with propofol and ketamine. J. vet. Pharmacol. Therap. doi: 10.1111/j.1365-2885.2012.01422.x. This study examined the pharmacokinetics of propofol by infusion in ponies using an analyser for th...
Article
Bonding, binding and isomerism influence the activity and elimination of many drugs. The bonding of drugs by tissues is dependent on their attraction and combination with cellular groups. Four main types of chemical bonds are involved (ionic bonds, dipole–dipole interactions, hydrogen bonds and covalent bonds). Ionic or electrostatic bonds are reve...
Article
Full-text available
The present study examines the molecular basis of induction of anaesthesia by i.v. hypnotic agents using comparative molecular field analysis (CoMFA). ED(50) induction doses for 14 i.v. anaesthetics in human subjects (expressed as molar dose per kilogram body weight) were obtained from the literature. Immobilizing potency data for the same 14 agent...
Article
There is uncertainty regarding the prognostic value of troponin and creatine kinase muscle and brain isoenzyme measurements after noncardiac surgery. The current study undertook a systematic review and meta-analysis. The study used six search strategies and included noncardiac surgery studies that provided data from a multivariable analysis assessi...
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Full-text available
The molecular basis of the cardiovascular effects of i.v. anaesthetics was investigated using comparative molecular field analysis (CoMFA). The cardiovascular effects, measured as changes in mean arterial pressure (MAP), compared with awake values of continuous infusions of 13 structurally diverse i.v. anaesthetics were compared at EC(50) plasma co...
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Full-text available
Recent studies of mechanisms of anaesthesia have been mainly ‘target orientated’, investigating the activity of both volatile and i.v. agents at putative sites of action. An alternative approach is one that is ‘ligand orientated’, focusing on the properties of molecules that define their immobilizing ability and secondly define their potency. The u...
Article
Aromatic anesthetics exhibit a wide range of N-methyl-d-aspartate (NMDA) receptor inhibitory potencies and immobilizing activities. We sought to characterize the molecular basis of NMDA receptor inhibition using comparative molecular field analysis (CoMFA), and compare the results to those from an equivalent model for immobilizing activity. Publish...
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BACKGROUND:The effect of carotid endarterectomy in lowering the risk of stroke ipsilateral to severe atherosclerotic carotid-artery stenosis is offset by complications during or soon after surgery. We compared surgery under general anaesthesia with that under local anaesthesia because prediction and avoidance of perioperative strokes might be easie...
Article
Much has been published about the impact of treatment on adverse outcomes in patients with cardiovascular diseases. Hypertension is an extremely common condition affecting a significant percentage of the world population. Although care guidelines exist for the medical patient with raised blood pressure, there are no accepted guidelines for the preo...
Article
During regional anesthesia for carotid endarterectomy (CEA), 10% to 15% of patients develop signs of cerebral hypoxia after cross-clamping, manifested as changes in speech, cerebration or contralateral motor power. Reversal of such neurological deficits using administration of 100% O2 has been described. We used near-infrared cerebral oximetry to a...
Article
Efforts to develop new hypnotic compounds continue, although several have recently failed in development. Propofol has been reformulated in various presentations with and without pre- servatives. Pharmacokinetic and pharmacodynamic differences exist between some of these preparations, and it is currently unclear whether any have substantial advanta...
Article
Administration of drugs to cats can be challenging and simple but effective techniques would be attractive to the owners. The purpose of this study was to compare the pharmacokinetics of buprenorphine (B) after buccal administration, and compare these to data previously collected from the same colony of cats after IV and IM injection. Twenty-four h...
Article
Propofol by infusion was administered to 6 adult beagle dogs on 2 separate occasions. The dogs received either no premedication or 20 μg/kg im medetomidine 15 min before induction of anaesthesia, with propofol given at 7 mg/kg/min to permit tracheal intubation. After tracheal intubation the infusion rate was maintained for 120 min at 0.4 mg/kg/min...
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Full-text available
Acute perioperative beta-adrenergic blockade may be cardioprotective in the high-risk cardiac patient for major non-cardiac surgery. We have investigated the association between the heart rate achieved with perioperative beta-blockade and the incidence of perioperative cardiac complications. We identified eight randomized studies (1931 patients) re...
Article
Bonding, binding and isomerism influence the activity and elimination of many drugs. The bonding of drugs by tissues is dependent on their attraction and combination with cellular groups. Four main types of chemical bonds are involved (ionic bonds, dipole–dipole interactions, hydrogen bonds and covalent bonds). Ionic or electrostatic bonds are reve...
Article
Full-text available
Background: The General Medical Council (GMC) is holding consultations in order to decide on the proposed changes to the undergraduate medical assessment. In the last round of consultation only eight medical students formally responded nationally. Aim: To determine the views of a larger proportion of final year medical students across the countr...
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The utility of interventional cardiology has developed significantly over the last two decades with the introduction of coronary angioplasty and stenting, with the associated antiplatelet medications. Acute coronary stent occlusion carries a high morbidity and mortality, and the adoption of therapeutic strategies for prophylaxis against stent throm...
Article
Six domestic shorthair cats, aged three to four years and weighing 5.1 to 7.4 kg, were used to assess the thermal antinociceptive effect of a transdermal buprenorphine patch, designed to supply 35 mug buprenorphine/hour, which was applied to the shaved thorax. The cats' thermal thresholds were tested before the patch was applied and two, four, six,...
Article
Ninety patients, premedicated with temazepam 20 mg, undergoing suction termination of pregnancy, were studied. Forty patients received alfentanil (500 μ g), and thirty halothane (1.5%) as supplements to either etomidate or methohexitone–nitrous oxide–oxygen anaesthesia. A further 20 patients received alfentanil 250 μg at induction of anaesthesia wi...
Article
An etomidate infusion was used to anaesthetise twelve patients for spinal surgery; six (group I) with 67% nitrous oxide and six (group II) with oxygen enriched air. Anaesthesia was induced with infused etomidate at a rate of 100 μg/kg/minute for 10 minutes and maintained at a rate of 10 μg/kg/minute. Recovery was assessed as the time to opening eye...
Article
Hepatic injury following repeat anaesthesia is a very rare but potentially fatal complication. The halogenated anaesthetic agents have been implicated in hepatic injury. Predisposing factors include repeat exposure to halogenated anaesthetics, genetic factors, middle age, female gender and liver enzyme induction. Halothane is a well-known cause of...
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Full-text available
Atherosclerosis is a common condition in both the developed and developing world and is now recognised to be an inflammatory condition leading to the development of ischaemic heart disease, cerebrovascular disease and peripheral vascular disease. Ischaemic heart disease is a major risk factor in the pathogenesis of perioperative adverse cardiovascu...
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We conducted a pharmaco-economic analysis of the prospective peri-operative studies of beta-blocker and statin administration for major elective non-cardiac surgery, using the Discovery Health claims costs for 2004. This analysis shows that acute peri-operative beta-blockade and statin therapy could result in a cost saving through a reduction in ma...
Article
Peri-operative beta-blockade has been shown to reduce the incidence of postoperative cardio- vascular complications including cardiac death in high-risk non-cardiac surgical patients. However, the recent analysis by Lindenauer et al. suggests that it is inappropriate to administer beta-blockers blindly to all surgical patients. In an attempt to det...
Article
We investigated the molecular basis for the immobilizing activity of halogenated volatile anesthetics using comparative molecular field analysis. In vivo potency data (expressed as minimum alveolar concentrations) for 69 structurally diverse anesthetics were obtained from the literature. The drugs were randomly divided into a training set (n = 52)...
Article
It is widely recommended that beta-blockade be used peri-operatively as it may reduce the incidence of postoperative cardiovascular complications including death. However, there are few data concerning the cost-effectiveness of such strategies. We have analysed the pharmacoeconomics of acute beta-blockade using data from eight prospective peri-oper...
Article
We analysed the pharmaco-economics of the prospective peri-operative studies of statin administration for major elective vascular surgery, using the NHS reference costs for 2004. This analysis suggests that peri-operative statin therapy for patients undergoing vascular surgery may present the most cost-effective use of statin therapy yet described,...
Article
Statin cardiovascular protection is mediated by lipid lowering and pleiotropic effects. The efficacy of statins has been established in non-surgical patients with cardiovascular disease and also more recently in non-surgical patients who sustain an acute coronary event. Peri-operative statin administration has been shown to improve both short-term...
Article
The pharmacokinetics and thermal antinociceptive effects of buprenorphine after intravenous (i.v.) or oral transmucosal (OTM) administration were studied in six adult cats. Plasma buprenorphine concentrations were measured using radioimmunoassay in a crossover study after a dose of 20 microg/kg given by the i.v. or OTM route. Oral pH was measured....
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Knowledge about UK doctors' career intentions and pathways is essential for understanding future workforce requirements. The aim of this study was to report career choices for and career progression in anaesthesia in the UK. Postal questionnaire surveys were undertaken of qualifiers from all UK medical schools in nine qualification years since 1974...
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The development of perioperative acute renal failure is associated with a high incidence of morbidity and mortality. Although this incidence varies with different surgical procedures and with the definition used for renal failure, we now understand better the aetiology of the underlying problem. However, successful strategies to provide renal prote...
Article
Data allowing rational use of analgesics in cats are limited. Pharmacokinetics and pharmacodynamics of fentanyl were studied in cats. Plasma fentanyl concentrations were measured using radioimmunoassay in a crossover study in six cats after 10 microg/kg (i.v.) or by application of fentanyl in pluronic lecithin organogel (PLO) to the inner ear pinna...
Article
To assess the incidence of major cardiac events in critically ill patients with a high risk of cardiac complications presenting with an elevated heart rate. Observational, retrospective study in a 15-bed medical/surgical Intensive Care Unit (ICU) at a university hospital for a period of 12 months. We studied patients with a high risk of cardiac com...
Article
We investigated the molecular basis for the immobilizing activity of nonhalogenated volatile anesthetics by using comparative molecular field analysis (CoMFA). In vivo potency data (expressed as minimum alveolar anesthetic concentrations) for 38 structurally diverse drugs were obtained from the literature. The anesthetics were randomly divided into...
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Full-text available
We reviewed the pathophysiology and treatment of hypertension in a recent edition of this journal (see key references). In this article, we discuss the management of the hypertensive patient presenting for surgery and anaesthesia.
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In summary, it is clear that perioperative myocardial infarction is a significant issue in patients undergoing vascular surgery. While the incidence of perioperative cardiac complications may be lower in patients undergoing other types of non-cardiac surgery, there are many more of these patients and their impact on the population burden of disease...
Article
To determine if increased QT interval dispersion (corrected and not corrected for heart rate) is associated with perioperative silent myocardial ischemia or postoperative adverse cardiovascular events. Blinded retrospective observational study. University hospital. One hundred eighty-one perioperative patients receiving general anesthesia for elect...
Article
Little is known about the effect of chronic beta-adrenoceptor antagonist therapy during the peri-operative period in patients undergoing non-cardiac surgery. We conducted a literature review to identify studies examining the relationship between chronic therapy and adverse peri-operative outcome. Eighteen studies were identified in which it was pos...
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Full-text available
Arterial hypertension is a major cause of morbidity and mortality because of its association with coronary heart disease, cerebrovascular disease and renal disease. The extent of target organ involvement (i.e. heart, brain and kidneys) determines outcome. North American studies have shown that hypertension is a major contributor to 500 000 strokes...
Article
We have previously demonstrated that the peri-operative measurement of increased serum concentrations of the cardiac markers troponins I and T and creatine kinase-MB can be predictors of major cardiovascular outcomes (including cardiac death) at 3 months after surgery. In the present study, we have followed the postoperative course of 157 patients...
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The evidence for an association between hypertensive disease, elevated admission arterial pressure, and perioperative cardiac outcome is reviewed. A systematic review and meta‐analysis of 30 observational studies demonstrated an odds ratio for the association between hypertensive disease and perioperative cardiac outcomes of 1.35 (1.17–1.56). This...
Article
Techniques, for detecting when patients undergoing surgery for hip fracture need more fluid, may reduce hospital stay, but more research is needed. Hip fracture is common, and the outcome may be poor. Many patients need more fluid, but clinicians find it difficult to tell how much is needed. Protocols (formal guidance) or advanced monitoring techni...
Article
Full-text available
The molecular basis of i.v. general anaesthetic activity was investigated using comparative molecular field analysis (CoMFA). The free plasma concentrations that abolish movement to a noxious stimulus for 14 structurally diverse i.v. anaesthetics were obtained from the literature. The compounds were randomly divided into a training set (n=10) to de...

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