Sunit Ghosh

Endotoxin-induced organ injury

ObjectiveTo review the effects of endotoxemia on the major organ systems of the body and discuss potential mechanisms of tissue injury. DesignAppraisal of 60 articles representing a cross section of studies relating to in vivo and in vitro responses to endotoxin. Main MethodsCell cultures, isolated tissue preparations, animal and human studies. ResultsEndotoxemia results in the activation of numerous cellular and hematogenous mediators. These mediators range from prostaglandins, thromboxanes, and leukotrienes, to complement components. Tumor necrosis factor may be responsible for initiating many of the observed responses to endotoxin. Species and tissue specificity are a prominent feature of the response to endotoxin. ConclusionsNo single agent can yet be implicated as the common mediator of endotoxin-induced organ injury. Endotoxin initiates the elaboration of a cascade of secondary mediators that amplify the response to the initial insult. The relative importance of individual agents as mediators of the response to endotoxin varies with the experimental model studied. (Crit Care Med 1993; 21:S19-S24)

Intra-articular bupivacaine: potentially chondrotoxic?

The management of acute postoperative pain after orthopaedic surgery is a challenge for anaesthetists and surgeons. The administration of local anaesthetic drugs into the joint space, either by single injection or by continuous infusion, has become a well-recognized technique for postoperative analgesia, in particular after arthroscopic surgery. Bupivacaine is commonly used for intra-articular analgesia because of its long duration of action. Other local anaesthetics used for intra-articular analgesia include ropivacaine and lidocaine. Intra-articular use of these drugs has been widely regarded as safe, and adverse effects of local anaesthetic agents in the joint space have been reported only rarely. Peak plasma concentrations of bupivacaine are sufficiently low after intra-articular injection such that systemic toxicity is extremely unlikely. However, overdose or inadvertent intravascular injection may result in central nervous system and cardiovascular toxicity. 3 Despite their widespread use, the effects of intra-articular local anaesthetic agents on joint structures have not been fully elucidated. Early evidence from animal experiments suggested that bupivacaine acutely inhibits the synthesis of articular cartilage. A later study found that intra-articular bupivacaine 0.5% resulted in articular cartilage inflammation and synovial membrane changes in rabbit knee joints. However, clinical reports of postoperative chondrolysis of the shoulder joint – 9 and ankle joint after arthroscopic surgery, and the possible association with the use of intra-articular bupivacaine, have brought the safety of intra-articular local anaesthetics to the fore among orthopaedic surgeons. Chondrolysis is a condition in which extensive loss of articular cartilage occurs over a relatively short period of time. After arthroscopic shoulder surgery, the consequences of postoperative glenohumeral chondrolysis are clearly devastating. The condition typically occurs in young athletes and effective treatment options are limited. The pain and reduced mobility associated with chondrolysis tend to progress to severe osteoarthritis, which may eventually require joint arthroplasty. The largest series of cases of post-arthroscopic glenohumeral chondrolysis (PAGCL) described 12 cases. The authors state that the common factor in all cases was the postoperative administration of an intra-articular infusion of bupivacaine with epinephrine. In total, 27 cases of PAGCL have been reported, with 25 of these cases having received postoperative continuous intra-articular analgesia with bupivacaine. – 9 Recently, a number of experimental studies have suggested that local anaesthetics may damage articular cartilage. It has been shown that bupivacaine 0.5% is toxic to both bovine articular chondrocyte cultures and bovine articular osteochondral tissue. The effect of bupivacaine on human cartilage has also been analysed. The effects of bupivacaine 0.5%, bupivacaine 0.25%, bupivacaine 0.125%, and saline 0.9% on bovine and human articular chondrocyte cultures were compared. Both bupivacaine 0.5% and bupivacaine 0.25% displayed dose-dependent and time-dependent chondrotoxicity. The toxicity of bupivacaine 0.5% was more marked than bupivacaine 0.25% at all time points. The toxicity of both drugs increased as the duration of exposure increased (from 15 to 60 min) and as the time after exposure increased (from 1 h to 1 week). The effect of bupivacaine 0.125% on bovine and human articular chondrocytes was no different from 0.9% saline. The effects of different concentrations of bupivacaine on bovine articular osteochondral tissue were also compared. Again, both bupivacaine 0.5% and bupivacaine 0.25% demonstrated dose-dependent chondrotoxicity. However, the effect of bupivacaine 0.125% was not different from 0.9% saline. Although less profound than the effects of bupivacaine, lidocaine 1% and lidocaine 2% also exhibit dosedependent and time-dependent toxic effects on bovine articular chondrocytes. Ropivacaine is the third local anaesthetic to be associated with chrondrotoxicity. The effects of bupivacaine 0.5% and ropivacaine 0.5% on both human articular chondrocyte cultures and human articular

A review of enhanced recovery for thoracic anaesthesia and surgery

During the past decade, there has been a dramatic increase in the number of thoracic surgical procedures carried out in the UK. The current financial climate dictates that more efficient use of resources is necessary to meet escalating demands on healthcare. One potential means to achieve this is through the introduction of enhanced recovery protocols, designed to produce productivity savings by driving reduction in length of stay. These have been promoted by government bodies in a number of surgical specialties, including colorectal, gynaecological and orthopaedic surgery. This review focuses on aspects of peri‐operative care that might be incorporated into such a programme for thoracic anaesthesia, for which an enhanced recovery programme has not yet been introduced in the UK, and a review of the literature specific to this area of practice has not been published before. We performed a comprehensive search for published work relating to the peri‐operative management and optimisation of patients undergoing thoracic surgery, and divided these into appropriate areas of practice. We have reviewed the specific interventions that may be included in an enhanced recovery programme, including: pre‐optimisation; minimising fasting time; thrombo‐embolic prophylaxis; choice of anaesthetic and analgesic technique and surgical approach; postoperative rehabilitation; and chest drain management. Using the currently available evidence, the design and implementation of an enhanced recovery programme based on this review in selected patients as a package of care may reduce morbidity and length of hospital stay, thus maximising utilisation of available resources.

Management of donors for heart and heart–lung transplantation

The quality of donor organs will determine the quality of life for the recipient and the importance of optimal management of the multi‐organ donor is that the organs may benefit up to five, critically ill, patients. The basic principle is to maintain sufficient preload to minimise the need for inotropic support and it is recommended that all multiple organ donors should have central venous and arterial pressure monitoring in addition to adequate venous access. The importance of the choice of fluid for volume expansion and the management of the hormonal disturbances which follow brain death are considered.

Assessment of Spatially Resolved Spectroscopy During Cardiopulmonary Bypass

Controversy remains about which tissue is primarily responsible for light attenuation of near infrared spectroscopy (NIRS) in the adult, the spatial resolution provided and the preferred algorithm for quantification. Until recently, changes in NIRS have not been fully quantified and have been difficult to interpret without sophisticated computation. A new development by Hamamatsu Photonics, the spatially resolved spectrometer (SRS), may be able to give a quantitative measure of oxygen saturation. We have incorporated the SRS into a multimodality monitoring system for the purpose of direct validation against jugular bulb oxygen saturation (SjO2) in patients undergoing routine cardiopulmonary bypass (CPB). The importance of this investigation is in the development of the SRS machine which shows potential as a useful clinical tool. The results demonstrated good correlation between SRS and SjO2 in 12 out of the 24 patients studied. Although these results are encouraging, this study suggests that the SRS, in its present form, is not a reliable clinical monitor of cerebral oxygen saturation during CPB.

Anti-D-coated Rh-positive red cells will bind the first component of the complement pathway, C1q

Human antibodies against the Rh blood group antigens do not in general activate the complement system. Rare reports of activation are restricted to either anti-D of certain sera bound to enzymetreated red cells [ 1,2] or to anti-D bound to papaintreated red cell stroma [3]. Since Clq must bind through 2 of its 6 heads to 2 separate IgM molecules on the cell surface [4-61, it has been suggested that anti-D molecules are too far apart on the red cell surface to allow Cl q to bind by two binding sites [7]. An alternative explanation is that Cl is able to bind to IgG anti-D on the cell surface but that there is failure in the subsequent activating steps. To differentiate between these 2 possibilities, the ability of 1251-labelled Cl q to bind anti-D coated red cells was investigated.

Dopexamine hydrochloride: pharmacology and use in low cardiac output states.

T HE TERM “INOTROPE” is broadly used to describe agents that enhance cardiac performance, although the mechanism by which some of these drugs improve myocardial function may be attributable less to their effect on myocardial contractility than to the other hemodynamic changes that are associated with their use. In the treatment of cardiac failure, agents with pharmacodynamic profiles that combine relatively mild direct effects on the myocardium with those resulting from a relatively greater effect on preload and afterload offer potential benefits from the standpoint of myocardial energy use. This is of prime concern in both the acutely or chronically ischemic heart and following cardiopulmonary bypass (CPB) when cardiac failure can, on occasion, be ascribed more to unavailability of energy reserves than to persisting ischemia. Dopexamine hydrochloride, a synthetic analog of dopamine, is characterized by just such a profile of action and may offer a favorable alternative to the more established therapeutic regimens of dopamine and dobutamine. The pharmacology of dopexamine and its use in the treatment of chronic or postoperative cardiac failure is reviewed here.

The Papworth BiVent tube: a feasibility study of a novel double-lumen endotracheal tube and bronchial blocker in human cadavers.

BACKGROUND A novel double-lumen endotracheal tube, the Papworth BiVent tube, has been designed to allow the rapid passage of a blocker into either main bronchus, without fibreoptic endoscopic guidance. METHODS The feasibility of lung isolation and one-lung ventilation (OLV) in human cadavers is examined, along with displacement of the bronchus blocker during head and neck movement. RESULTS Cadaveric endotracheal intubation with the Papworth BiVent tube was straightforward and comparable with intubation with a conventional single-lumen tube (SLT). Reliable lung isolation was achieved considerably faster using the Papworth BiVent tube than with a bronchoscopically guided bronchial blocker through an SLT (mean 7.75 s BiVent tube vs 128.2 s SLT). The Papworth BiVent tube also prevented displacement of the blocker from its position in the bronchus on head movement. CONCLUSIONS This study in human cadavers has shown that it is feasible to use the Papworth BiVent tube to attain rapid and secure lung isolation for OLV. Further work is required in clinical settings.

The Papworth BiVent tube : a new device for lung isolation

Provision of one lung ventilation can be technically challenging, particularly for anaesthetists who are only occasionally required to isolate one lung from the other. A new double lumen endotracheal tube, the Papworth BiVent Tube, has been designed to enable rapid and reliable lung isolation using any bronchus blocker without the need for fibreoptic endoscopic guidance. In this study, an airway‐training manikin was used to assess ease of tracheal intubation and lung isolation using the Papworth BiVent tube. Ease of intubation was compared to a single lumen endotracheal tube and a conventional double lumen endobronchial tube. Ease of lung isolation when using a bronchus blocker was compared to a single lumen tube combined with a bronchial blocker. Tracheal intubation using the Papworth BiVent tube was found to be easier than when using a conventional double lumen endobronchial tube. Lung isolation using the Papworth BiVent tube used in combination with a bronchus blocker was achieved more reliably and rapidly than when using a single lumen tube and bronchus blocker.

NICE guidance on CardioQ

ical Technologies Advisory Committee considers all the features of trial evidence, irrespective of funding source, on the basis of quality, robustness, quantity and potential sources of bias. Ghosh et al. also point out that outcome measures and patient groups were heterogeneous among the available studies; in our experience, this is a common characteristic of clinical evidence, which is why we have developed a deliberative, structured and balanced approach to decision-making. The wide range of clinicians, scientists, lay people and other disciplines on MTAC aims to provide the necessary skills and expertise to weigh evidence and other factors, and to make difficult judgements. The advice of clinical experts is a very important part of the information available to the Committee in making its recommendations. Experts are nominated by stakeholders, including professional societies and manufacturers, and there are robust processes for managing conflicts of interest. We encourage specialist clinicians, including Ghosh and colleagues, to become involved in future medical technology evaluations by seeking to be nominated as experts in their specialty. We would also encourage clinical experts to respond to public consultation, which is a very influential step in the production of NICE guidance.