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Biomedical subjects

J F Bion

Publications and source records attributed to J F Bion.

At least 19 recordsLinked to original sources

Susceptibility to critical illness: reserve, response and therapy.

Risk of critical illness is determined both by genetic and environmental influences, particularly those relating to infectious and cardiovascular diseases. Physiologically-based scoring systems cannot measure prior risk because they do not quantify physiological reserve independently of the acute illness. Genetic profiling could be useful for risk assessment. Early detection of critical illness involves identifying physiological 'triggers' for referral; this requires the education of nursing and medical staff in their significance. Analysis of the relationship between risk factors and interventions may need complex modelling techniques. Therapeutic strategies depend on the nature of the underlying problem: the most useful are likely to be those which enhance tissue oxygen delivery and resistance to infection.

Critical Care↗

Is the gut responsible for multiple organ failure?

Multiple organ failure is the consequence of many pathological processes, an acute reduction in oxygen supply being one of the most important. The splanchnic region is particularly susceptible to hypoxic injury, and the ischaemic gut mucosa may act as a neutrophil activating site. This is followed by leukocyte adhesion to endothelium and migration into the tissues where cytotoxic chemicals are released, producing tissue injury. This process is aggravated by multiple and sequential physiological insults, some of which may not be evident using basic clinical monitoring. The factors which precipitate cell injury and organ failures may be amenable to relatively simple preventative interventions, but once damage has occurred the process becomes increasingly complex and self-sustaining. Natural defence systems may become pathologically hyperactive, or suppressed, at different stages in critical illness, making it difficult to target therapies directed at the immunoinflammatory cascade with any degree of accuracy or safety, explaining in part the failure of immunotherapy for sepsis. There are significant genetic and constitutional components to susceptibility to critical illness, the most important of which affect cardiac reserve and the ability to maximise tissue oxygen supply. Whether the gut is the most important target organ for oxygen delivery in stress is still the subject of continued research.

Digestive System↗

Basic life support training for health care students.

This paper describes a novel method for delivering basic life support training to undergraduate healthcare students. A comprehensive 8 h programme is organised and delivered by undergraduate students to their peers. These students have undergone training as basic life support instructors validated by the Royal Life Saving Society UK. The course is delivered to multiprofessional groups of medical, dental, physiotherapy, biomaterial and nursing undergraduates. It has been well received by students and academic staff and provides a solution to reduce the workload of over burdened clinical staff while at the same time enhancing quality. It forms part of an overall strategy for improving resuscitation training for undergraduates from all disciplines.

Cardiopulmonary Resuscitation↗

Epidemiology of intensive care medicine: supply versus demand.

Developments in hospital medicine combined with social and demographic changes are likely to increase the need for intensive care services at a time when cost containment and cost-efficacy are the main items on the political agenda. This will exaggerate the supply-demand outcome mismatch unless the problem is approached in a constructive manner by clinicians, managers and politicians. More resources will be required for intensive care, but these must be better targeted and more efficiently employed. Opportunities for prevention should be explored, with intensive care being given a pro-active rather than a re-active role. Intensive care clinicians should understand that this expanded role cannot be achieved if they are willing only to accept responsibility for patient care after the patient has been admitted to the ICU. Clinicians and managers should develop methods for linking the various disciplines which contribute to emergency care, to form an acute care framework within the hospital. Research into the factors which determine risk of critical illness should be combined with enhanced medical and nursing training in intensive care, accompanied by an expansion in resources for intermediate and high dependency care in countries like the UK where there is clear evidence of rationing.

Critical Care↗

Intensive care training and specialty status in Europe: international comparisons. Task Force on Educational issues of the European Society of Intensive Care Medicine.

OBJECTIVE: To describe current arrangements for postgraduate training and speciality status for intensive care medicine in Europe, and to compare these with three other geographical regions: the Middle East, North America, and Australia and New Zealand. METHODS: An iterative survey, by questionnaire and direct discussion, of council members of the European Society of Intensive Care Medicine, national specialist societies with involvement in intensive care, and national experts, representing four geographical regions and 47 countries. RESULTS: For the purposes of analysis, countries with common training structures have been grouped together; the denominator therefore includes both countries and regions. Formal training programmes in intensive care medicine (ICM) are available in 18 (85%) of the 21 countries or regions surveyed. Twelve (57%) offer multidisciplinary access to intensive care training with a common core curriculum. In six (28%) training in ICM is available solely through anaesthesia. The duration of intensive care training required for recognition as a specialist in the 18 countries or regions with a formal programme ranges from 18 to 30 months, with a median of 24 months. All countries assess competence in intensive care, but methods for doing so vary widely. Eighteen countries or regions offer specialist registration (accreditation) in ICM; in 12 this is provided as dual accreditation in a base speciality and in ICM. CONCLUSIONS: There is substantial support for multidisciplinary training in ICM, as demonstrated by collaborative interspeciality developments in many countries. We propose that these national developments should be strengthened within Europe by the recognition of 'supra-speciality' status for ICM by the European Commission, and by the establishment of a multidisciplinary Board for training in ICM, with international agreement on core competencies and duration of training programmes, and a common approach to the assessment of competence through formal examination.

Accreditation↗

A comparison of cisatracurium (51W89) and atracurium by infusion in critically ill patients.

OBJECTIVE: To evaluate and compare the safety and efficacy of cisatracurium (51W89) and atracurium administered by continuous infusion to critically ill patients requiring neuromuscular blocking agents to facilitate mechanical ventilation. DESIGN: Open, randomized, multicenter study of patients receiving cisatracurium or atracurium infusion to facilitate mechanical ventilation. SETTING: Five university teaching hospital intensive care units in the United Kingdom. PATIENTS: Sixty-one adult patients requiring neuromuscular blocking agents to facilitate mechanical ventilation. INTERVENTIONS: Bolus doses followed by continuous infusions of cisatracurium or atracurium were administered. Onset, maintenance, and recovery of neuromuscular blockade were measured, using transcutaneous ulnar nerve stimulation and an accelerometer. MEASUREMENTS AND MAIN RESULTS: Forty patients received cisatracurium (mean duration 48.1 +/- 4.2 [SEM] hrs), and 21 patients received atracurium (mean duration 46.1 +/- 5.8 hrs). The infusion rate for patients receiving cisatracurium was 3.1 +/- 0.2 microg/kg/min, and for patients receiving atracurium 10.4 +/- 0.9 microg/kg/min. There were no significant differences in mean times to 70% recovery of Train-of-Four ratio (cisatracurium 60 mins, atracurium 57 mins), although there was considerable interpatient variation (20 to 175 mins with cisatracurium vs. 35 to 85 mins with atracurium). One patient who received cisatracurium exhibited intermittent bronchospasm during and after the study period. CONCLUSIONS: Cisatracurium, an isomer of atracurium, appears to be a suitable agent for providing muscle relaxation in critically ill patients.

APACHE↗

Intestinal permeability, gastric intramucosal pH, and systemic endotoxemia in patients undergoing cardiopulmonary bypass.

OBJECTIVE: To examine the relationship between gastric intramucosal pH, intestinal permeability, endotoxemia, and oxygen delivery in patients undergoing cardiopulmonary bypass (CPB). DESIGN: Prospective, observational study. SETTING: Tertiary care center. PATIENTS: Fifty patients undergoing elective cardiac surgery and 10 patients awaiting elective cardiac surgery. INTERVENTIONS: Patients received chromium 51-labeled ethylenediaminetetraacetic acid (51Cr-EDTA) as a marker of intestinal permeability; insertion of a nasogastric tonometer to measure intramucosal pH (pHi); insertion of a pulmonary artery catheter to measure systemic oxygen delivery and consumption variables; arterial blood sampling for plasma endotoxin by the Limulus amebocyte lysate assay; and blood and urine sampling for measurement of 51Cr-EDTA. MAIN OUTCOME MEASURES: Systemic oxygen delivery, duration of gastric mucosal acidosis, absorption of 51Cr-EDTA, appearance of systemic endotoxemia, renal dysfunction, and duration of hospital stay. RESULTS: Median (range) 24-hour urinary recovery of 51Cr-EDTA in patients was 10.6% (2.1% to 40.2%) while that in controls was 1.2% (0.7% to 2.0%, P<.001). Intestinal permeability increased during CPB. The median (range) for the lowest pHi after bypass was 6.98 (6.74 to 7.17). The pHi did not decline until CPB was discontinued and the heart took over the load of the circulation. Endotoxin was detectable (>0.2 endotoxin unit per milliliter) in the plasma of 21 patients (42%) during the study, most of whom were endotoxemic by the end of CPB. There was no evident relationship between the degree of gut permeability, endotoxemia, gut ischemia, or systemic oxygen dynamics. CONCLUSIONS: Cardiopulmonary bypass is associated with increases in gut permeability, which precede gut mucosal ischemia. In cardiac surgical patients, a low pHi is not necessarily indicative of an adverse clinical outcome. Endotoxemia as measured by the Limulus amebocyte lysate assay is common. The increased intestinal absorption of 51Cr-EDTA and gastric mucosal acidosis occur as independent phenomena and are not related in severity or time of onset.

Acidosis↗

The use of neuromuscular blocking drugs in intensive care practice.

Critically ill patients represent a very different population from that of the operating theatre, but much of our knowledge of many of the neuromuscular blocking drugs is derived from intraoperative use. The diversity of clinical-practice and case-mix differences in intensive care are probably responsible for the absence of a formal consensus about the use of neuromuscular blocking drugs in the intensive care unit (ICU). Various surveys suggest that these drugs are used comparatively infrequently, but we do not know whether current usage is either safe or appropriate. In addition to the adverse effects which inevitably accompany prolonged paralysis and immobility, the steroidal relaxants, pancuronium and vecuronium, have also been associated with myopathy. This seems to be aggravated by concurrent use of pharmacologic doses of corticosteroids or the aminoglycoside antibiotics. Neither the mechanism nor the validity of the association with steroidal relaxants is known at present. Muscle dysfunction is a common feature of critical illness, and it is possible that neuromuscular blocking drugs interfere with muscle repair and regrowth. Patients with multiple organ failure present a particular challenge both because of the extent of tissue injury and because drug clearance via the liver or kidneys is generally impaired.

Adrenal Cortex Hormones↗

Selective decontamination of the digestive tract reduces gram-negative pulmonary colonization but not systemic endotoxemia in patients undergoing elective liver transplantation.

OBJECTIVE: To examine the effect of selective antibiotic decontamination of the digestive tract in patients undergoing elective orthotopic liver transplantation. DESIGN: Prospective, randomized, concurrent allocation to either selective decontamination or standard antibiotic prophylaxis. SETTING: Operating theater and intensive care unit at a tertiary referral, university teaching hospital. PATIENTS: Fifty-nine adult patients were recruited into the study and underwent liver transplantation. INTERVENTIONS: Thirty-two patients were randomized to standard treatment (control group) and 27 patients were randomized to receive selective decontamination. After early deaths and exclusions, 31 controls and 21 decontamination patients were available for analysis. MEASUREMENTS AND MAIN RESULTS: Portal and systemic endotoxemia, colonization and infection rates, severity of illness (organ system failures, Acute Physiology and Chronic Health Evaluation II score, Therapeutic Intervention Scoring System score), antibiotic costs, and hospital survival rates were measured. Selective decontamination significantly reduced pulmonary infections and enteric, aerobic, and Gram-negative bacillary colonization without facilitating the emergence of resistant organisms, but selective decontamination had no effect on endotoxemia or the development of organ system failures. The financial costs of the selective decontamination regimen outweighed the advantages gained from an associated reduction in antibiotic usage. CONCLUSION: The failure of selective decontamination to enhance survival rates in many studies of the regimen in critically ill patients may, in part, be related to the inability of selective decontamination to abolish endotoxemia.

Adult↗

Antibiotic-induced release of endotoxin from bacteria in vitro.

The ability of cefotaxime, ciprofloxacin, piperacillin and tobramycin to cause release of endotoxin was examined in vitro with cultures of Enterobacter cloacae and Escherichia coli. Endotoxin was measured by a quantitative limulus amoebocyte lysate assay and its presence was confirmed by silver staining of the lipopolysaccharide moiety following SDS-PAGE. The morphology of the bacteria during antibiotic exposure was examined by scanning electronmicroscopy. Cefotaxime, ciprofloxacin and piperacillin caused significant endotoxin release, correlating with their ability to affect cell-wall morphology, causing filamentation, wall breakage and cell lysis. In contrast, little endotoxin was released when bacteria were exposed to tobramycin and no morphological changes were observed when bacteria were exposed to bactericidal concentrations of this aminoglycoside. Its antimicrobial spectrum and bactericidal activity make tobramycin an appropriate agent for treatment of sepsis caused by gram-negative bacteria and its lack of propensity to elicit excessive release of endotoxin may avoid exacerbation of endotoxin-related shock in sepsis.

Anti-Bacterial Agents↗

Atracurium infusions in patients with fulminant hepatic failure awaiting liver transplantation.

OBJECTIVE: To determine the pharmacokinetics and pharmacodynamics of the neuromuscular blocking agent atracurium besylate in patients with fulminant hepatic failure (FHF). DESIGN: Open study of patients receiving atracurium infusions to facilitate mechanical ventilation. SETTING: Intensive care unit in a tertiary referral university teaching hospital. PATIENTS: Ten encephalopathic patients with FHF requiring mechanical ventilation while awaiting orthotopic liver transplantation. Three patients died before transplantation could be performed, three died after transplantation, and four survived following successful transplantation. METHODS: Plasma, urine and dialysate fluid were analysed for atracurium and its metabolites using HPLC. Neuromuscular blockade was measured using transcutaneous ulnar nerve stimulation and an accelerometer. Electroencephalography and liver function tests were performed daily. RESULTS: Patients received atracurium infusions for a period ranging from 38 to 217 h. Six patients required continuous arteriovenous haemodiafiltration (CAVHD) to replace renal function. Atracurium mean steady state clearance was 8.6 ml/min/kg, and train-of-four recovery ratio to 75% took 63 min (range 32-108). Laudanosine clearance was markedly reduced in the non-survivors; the half-life was 38.5 hrs compared with 5.3 h in the 4 patients who underwent successful transplantation. Laudanosine accumulation could be observed in all patients before transplantation, but kinetics returned to normal after successful transplantation. The highest laudanosine level recorded was 6,860 ng/ml. There was no evidence of adverse central neurological effects attributable to laudanosine. CAVHD did not contribute significantly to clearance of atracurium or its metabolites. CONCLUSIONS: Atracurium kinetics and dynamics are near-normal even in patients with fulminant hepatic failure and renal failure; laudanosine accumulation will occur, but this is not associated with measurable central neurological effects. Implantation of a functioning liver graft results in clearance of laudanosine, which seems to be independent of renal function. Atracurium is an appropriate choice for producing neuromuscular blockade for periods of several days in patients with fulminant hepatic failure and renal impairment.

Adult↗