Validation of the factors influencing family consent for organ donation in the UK.

Between 2013 and 2019, there was an increase in the consent rate for organ donation in the UK from 61% to 67%, but this remains lower than many European countries. Data on all family approaches (16,896) for donation in UK intensive care units or emergency departments between April 2014 and March 2019 were extracted from the referral records and the national potential donor audit held by NHS Blood and Transplant. Complete data were available for 15,465 approaches. Consent for donation after brain death was significantly higher than for donation after circulatory death, 70% (4260/6060) vs. 60% (5645/9405), (OR 1.58, 95%CI 1.47-1.69). Patient ethnicity, religious beliefs, sex and socio-economic status, and knowledge of a patient's donation decision were strongly associated with consent (p < 0.001). These factors should be addressed by medium- to long-term strategies to increase community interventions, encouraging family discussions regarding donation decisions and increasing registration on the organ donor register. The most readily modifiable factor was the involvement of an organ donation specialist nurse at all stages leading up to the approach and the approach itself. If no organ donation specialist nurse was present, the consent rates were significantly lower for donation after brain death (OR 0.31, 95%CI 0.23-0.42) and donation after cardiac death (OR 0.26, 95%CI 0.22-0.31) compared with if a collaborative approach was employed. Other modifiable factors that significantly improved consent rates included less than six relatives present during the formal approach; the time from intensive care unit admission to the approach (less for donation after brain death, more for donation after cardiac death); family not witnessing neurological death tests; and the relationship of the primary consenter to the patient. These modifiable factors should be taken into consideration when planning the best bespoke approach to an individual family to discuss the option of organ donation as an end-of-life care choice for the patient.

Current status of organ donation after brain death in the UK.

Organ donation after brain death remains the deceased organ donation pathway of choice. In the UK, the current identification and referral rate for potential donation after brain death donors is 99%, the testing rate for determining death using neurological criteria is 86% and the approach to families for donation is 91%. Increasing donation after brain death donation will primarily require a large increase in the current consent rate of 72% to one matching the consent rate of 80-90% achieved in other European countries. Implementing the use of evidence-based donor optimisation bundles may increase the number of organs available for transplantation. Alternatively, the UK will need to look at more challenging ways of increasing the pool of potential donors after brain death. The first would be to delay the withdrawal of life-sustaining treatment in patients with devastating brain injury to allow progression to brain death after the family have given consent to organ donation and with their consent to this delay. Even more challenging would be the consideration of re-introducing intensive care to facilitate organ donation programmes that have been so successful at increasing the number of organ donors elsewhere.

Organ donation after circulatory death: current status and future potential.

The continuing shortage of deceased donor organs for transplantation, and the limited number of potential donors after brain death, has led to a resurgence of interest in donation after circulatory death (DCD). The processes of warm and cold ischemia threaten the viability of DCD organs, but these can be minimized by well-organized DCD pathways and new techniques of in situ organ preservation and ex situ resuscitation and repair post-explantation. Transplantation survival after DCD is comparable to donation after brain death despite higher rates of primary non-function and delayed graft function. Countries with successfully implemented DCD programs have achieved this primarily through the establishment of national ethical, professional and legal frameworks to address both public and professional concerns with all aspects of the DCD pathway. It is unlikely that expanding standard DCD programs will, in isolation, be sufficient to address the worldwide shortage of donor organs for transplantation. It is therefore likely that reliance on extended criteria donors will increase, with the attendant imperative to minimize ischemic injury to candidate organs. Normothermic regional perfusion and ex situ perfusion techniques allow enhanced preservation, assessment, resuscitation and/or repair of damaged organs as a way of improving overall organ quality and preventing the unnecessary discarding of DCD organs. This review will outline exemplar controlled and uncontrolled DCD pathways, highlighting practical and logistical considerations that minimize warm and cold ischemia times while addressing potential ethical concerns. Future perspectives will also be discussed.

Factors influencing the family consent rate for organ donation in the UK.

The refusal rate for organ donation in the UK is 42%, among the highest in Europe. We extracted data on every family approach for donation in UK ICUs or Emergency Departments between 1st April 2012 and 30th September 2013, and performed multiple logistic regression to identify modifiable factors associated with consent. Complete data were available for 4703 of 4899 approaches during the study period. Consent for donation after brain death was 68.9%, and for donation after circulatory death 56.5% (p < 0.0001). Patient ethnicity, knowledge of a patient's wishes and involvement of a specialist nurse in organ donation in the approach were strongly associated with consent (p < 0.0001). The impact of the specialist nurse was stronger for donation after circulatory death than for donation after brain death, even after accounting for the impact of prior knowledge of patients' wishes. Involvement of the specialist nurse in the approach, encouraging family discussions about donation wishes and promotion of the organ donor register are key strategies to increase UK consent rates, and are supported by this study.

Role of therapeutic hypothermia in improving outcome after traumatic brain injury: a systematic review.

This systematic review delineates the effect of primary therapeutic hypothermia (PTH) (initiated on presentation of the patient) on both mortality and neurological outcome in patients with traumatic brain injury. The safety profile of the therapy is also assessed. A systematic search of the following databases was performed: MEDLINE, EMBASE, Zetoc database of conference proceedings, the Cochrane Database of Systematic Reviews, and the clinicaltrials.gov website, up to July 28, 2011. Relevant journals were hand-searched for further articles and reference lists were checked against the retrieved results for additional resources. The retrieved results were filtered for randomized controlled trials in English where systemic hypothermia was applied for ≥ 12 h in the treatment arm and outcome was assessed at a minimum of 3 months. Randomized controlled trials were assessed for quality of evidence using the GRADE system. Eighteen randomized controlled trials (1851 patients) were identified. The overall relative risk of mortality with PTH when compared with controls was 0.84 [95% confidence interval (CI)=0.72-0.98] and of poor neurological outcome was 0.81 (95% CI=0.73-0.89). However, when only high-quality trials were analysed, the relative risks were 1.28 (95% CI=0.89-1.83) and 1.07 (95% CI=0.92-1.24), respectively. Hypothermia was associated with cerebrovascular disturbances on rewarming and possibly with pneumonia in adult patients. Given the quality of the data currently available, no benefit of PTH on mortality or neurological morbidity could be identified. The therapy should therefore only be used within the confines of well-designed clinical trials.

Donation after circulatory death.

Donation after circulatory death (DCD) describes the retrieval of organs for the purposes of transplantation that follows death confirmed using circulatory criteria. The persisting shortfall in the availability of organs for transplantation has prompted many countries to re-introduce DCD schemes not only for kidney retrieval but increasingly for other organs with a lower tolerance for warm ischaemia such as the liver, pancreas, and lungs. DCD contrasts in many important respects to the current standard model for deceased donation, namely donation after brain death. The challenge in the practice of DCD includes how to identify patients as suitable potential DCD donors, how to support and maintain the trust of bereaved families, and how to manage the consequences of warm ischaemia in a fashion that is professionally, ethically, and legally acceptable. Many of the concerns about the practice of both controlled and uncontrolled DCD are being addressed by increasing professional consensus on the ethical and legal justification for many of the interventions necessary to facilitate DCD. In some countries, DCD after the withdrawal of active treatment accounts for a substantial proportion of deceased organ donors overall. Where this occurs, there is an increased acceptance that organ and tissue donation should be considered a routine part of end-of-life care in both intensive care unit and emergency department.

Experiences in the development of non-heart beating organ donation scheme in a regional neurosciences intensive care unit.

BACKGROUND: In the UK demand for organ transplantation continues to outstrip supply and one strategy aimed at reversing this trend is the introduction of non-heart beating donor (NHBD) schemes. In this paper we describe our experience after the introduction of the NHBD scheme at a regional neuroscience intensive care unit (ICU) that also provides general intensive care. METHODS: We describe the steps taken to establish the scheme and present our results from the time of its implementation in July 2002 until March 2007. RESULTS: Of the 100 patients whom we referred to the transplant co-ordinators, 71 were identified as potential NHBDs and of these 29 went on to become actual donors (conversion rate of 40.8%). Fifty-six kidneys were retrieved and 53 successfully transplanted. In addition, two livers were retrieved but subsequently found to be unsuitable for transplantation, while eight pancreas were retrieved and used for islet cell research. The serum creatinine at 1 yr demonstrates that there is no significant difference between transplanted kidney function from NHBDs and heart-beating donors (HBDs). CONCLUSIONS: We believe that by establishing the NHBD organ donation scheme we are able to fulfil the wishes of more patients who have indicated that they would like to donate their organs while increasing the availability of solid organs for transplantation. With careful preparation, audit, and communication our experience demonstrates that the NHBD scheme can be successfully introduced in an ICU and expanded to other ICUs in a region.

Mortality from percutaneous dilatational tracheostomy. A report of three cases.

We report three deaths following percutaneous dilatational tracheostomy in a series of 1187 procedures undertaken in a single intensive care unit over a 13-year period. All deaths were due to severe haemorrhage. The first patient died during the procedure from uncontrollable haemorrhage from the innominate vein. Delayed haemorrhage in the other two patients was caused by the tracheostomy tube eroding into the aorta in one patient and into the innominate vein in the other. In both these patients, the tracheal stoma was found at postmortem to be sited unexpectedly low. Fatal haemorrhage is a rare complication of percutaneous tracheostomy (0.25% in this series), but is probably under-reported. While bronchoscopy is now used routinely during percutaneous tracheostomy insertion in most units, we speculate that ultrasound examination of the neck is more likely to identify major vascular structures at risk. However, whilst intuitive, there is little evidence that either bronchoscopy or ultrasound scanning reduces the incidence of complications. Magnetic resonance images of normal subjects are presented to demonstrate the anatomical relations of the trachea to major vascular structures and their variability.

Reduction in mortality from severe head injury following introduction of a protocol for intensive care management.

BACKGROUND: To determine the effect of an intensive care management protocol on the intensive care unit (ICU) and hospital mortality of severely head-injured patients, we designed a longitudinal observational study of all patients admitted with a head injury between 1992 and 2000. METHODS: A computerized patient database was used to identify all patients with severe head injury admitted to the ICU at Frenchay Hospital, Bristol, UK: a tertiary referral centre for the clinical neurosciences. We compared the ICU and hospital mortality and length of stay in patients before and after implementation of a protocol for their ICU management in 1997. RESULTS: Implementation of the protocol was associated with a significant reduction in ICU mortality from 19.95% to 13.5% (odds ratio 0.47; 95% CI 0.29-0.75), and in hospital mortality from 24.55% to 20.8% (odds ratio 0.48; 95% CI 0.31-0.74). This was achieved despite a significant increase in the median APACHE II score (14 vs 18) of patients admitted after implementation of the protocol. The median ICU and hospital length of stay remained constant over the study period. CONCLUSIONS: The introduction of an evidence-based protocol to guide the ICU management of patients with severe head injury has been associated with a significant reduction in both ICU and hospital mortality.

Effect of propofol anaesthesia on the event-related potential mismatch negativity and the auditory-evoked potential N1.

BACKGROUND: Studies on the effects of anaesthesia on event-related potentials and long latency auditory-evoked potentials (AEP) are sparse. Both provide information on cortical processing and may have potential as monitors of awareness. We studied the effect of propofol on the event-related potential mismatch negativity (MMN) and the long-latency AEP NI. METHODS: Twenty-one patients received 1 microgram ml-1 stepped increases in the target concentration of propofol using Diprifusor until a maximum of 6 micrograms ml-1 was achieved or the patient had lost consciousness. Neurophysiological responses (MMN and N1) and the patients' level of consciousness were recorded before the administration of propofol and at a target effector site concentration of propofol of 1, 2, 3, 4, and 6 micrograms ml-1. Grand average evoked potentials were computed at baseline, before the administration of propofol (A); at the highest propofol concentration at which each patient was responsive (B); and at the concentration of propofol at which the patient became unconscious (C). RESULTS: Patients lost consciousness at different target concentrations of propofol, all being unresponsive by 4 micrograms ml-1. The response to the deviant stimuli used to elicit duration-shift MMN was significantly more negative than to the standard stimuli at A (mean difference 2.58 microV, P = 0.0011) but this difference was virtually abolished at point B, before the patients lost consciousness (mean difference 0.63 microV, P = ns). The amplitude of N1 evoked by standard stimuli was negative compared with electrical baseline at both point A (mean amplitude -3.81 microV, P < 0.001) and at point B (mean amplitude -2.2 microV, P = 0.002), but was no longer significantly different to baseline at point C (mean amplitude 0.51 microV, P = ns). The change in the mean amplitude of N1 from last awake (point B) to first unconscious (point C) was also significant (mean difference in amplitude 1.69 microV, P = 0.02). CONCLUSIONS: MMN is unlikely to be a clinically useful tool to detect awareness in surgical patients. In contrast, the loss of N1 may identify the transition from consciousness to unconsciousness and deserves further study.

Late deaths in multiple trauma patients receiving intensive care.

We reviewed the cause and timing of death of all the patients who died within hospital following multiple trauma and admission to a multidisciplinary intensive care unit (ICU) that also acts as a tertiary referral centre for neurosurgery. The ICU database identified 101 such patients in a 3-year period and their records were reviewed retrospectively. There were 40 (39%) deaths within 24 h of admission to the ICU, 38 of which resulted from severe brain injury and two from haemorrhagic shock (HS). A further 61 (60%) deaths occurred more than 24 h after the time of admission to ICU (mean 7 days; range 2-49 days), of which 46 (75%) were due to severe brain injury. While these findings do not question the promulgated tri-modal distribution of death following trauma, they are at variance with the view that the third peak of deaths is due mainly to multiple organ failure. When severe head injury accompanies multiple trauma, it is likely to be the major determinant of late mortality. If outcome from major trauma is to be improved, then a greater emphasis needs to be placed on the prevention and optimal management of severe brain injury.

Behaviour of near-infrared light in the adult human head: implications for clinical near-infrared spectroscopy.

To test theoretical assumptions supporting the use of near-infrared spectroscopy (NIRS) in clinical practice, we examined the behaviour of NIR light transmission and attenuation in the human head. Sterile probes for emitting and detecting NIR light at a fixed separation of 40 mm were placed in turn on intact skin, skull, dura and cerebral cortex of 10 patients undergoing elective neurosurgery. In the first five patients, the detecting probe was moved through successive extracerebral layers with the emitter on the skin surface. In the second five patients, the process was reversed, with the emitting probe moved and the detector in the same place on the scalp. NIR intensity was measured at each tissue interface and compared with the intensity measured at the skin surface with all layers intact. Removal of bone and dura from the light path caused a significant reduction in detected intensity. The largest mean reduction in light intensity was a 14-fold decrease with removal of bone (unadjusted P < 0.0001; paired t test). The assumptions that extracerebral tissues contribute little to attenuation of NIR light in the adult head and that most of this attenuation occurs superficially in the scalp are drawn into question by this study. We postulate that the skull and/or its interface with other layers may act as an optical 'channel', distorting the behaviour of NIR light in the human head.

Cerebral near infrared spectroscopy: emitter-detector separation must be increased.

We have compared the effect of increasing optode separation (range 0.7-5.5 cm) on the sensitivity of near infrared spectroscopy (NIRS) to discrete reductions in scalp and cerebral oxygenation in 10 healthy men (mean age 32, range 26-39 yr) using multichannel NIRS. During cerebral oligaemia (a mean reduction in middle cerebral artery flow velocity of 47%) induced by a mean reduction in end-tidal PCO2 of 2.4 kPa, the decrease in oxyhaemoglobin detected by NIRS became significantly greater with increasing optode separation (P < 0.0001). In response to scalp hyperaemia induced by inflation and release of a pneumatic scalp tourniquet, increases in oxyhaemoglobin became significantly smaller with increasing optode separation (P < 0.0002). These results are consistent with theoretical models of the behaviour of NIR light in the adult head and support the concept of using multi-detector NIRS to separate intra- and extracranial NIR signal changes. However, the emitter-detector separation used by currently available cerebral oximeters is not large enough to provide optimal spatial resolution.

The impact of percutaneous tracheostomy on intensive care unit practice and training.

We studied the impact of introducing percutaneous tracheostomy to our intensive care unit on the incidence and timing of tracheostomy and on the implications for surgical training. The proportion of patients receiving intensive care who underwent tracheostomy doubled from a median of 8.5% to 16.8% (p < 0.01) following the introduction of the percutaneous technique with the procedure being undertaken significantly earlier during the intensive care stay. The opportunity for surgical trainees to gain experience in open surgical tracheostomy has been virtually lost. The increase in tracheostomy rate may reflect a previous under-utilisation caused by the logistic problems of transferring a critically ill patient to theatre, or alternatively a relaxation of the indications for tracheostomy caused by a perceived benefit for the patient. An increased workload may also have contributed to the rise. Surgical trainees should be encouraged to learn percutaneous techniques and training opportunities in open surgical techniques should be maximised.

Percutaneous tracheostomy in the intensive care unit.

Percutaneous tracheostomy is now established in intensive care practice. However, discussion continues on many aspects of the procedure. This update reviews recent studies of bedside percutaneous tracheostomy, which suggest that the commonly used techniques are safe in terms of short and long-term complications. The introduction of percutaneous tracheostomy into an intensive care unit has training implications, particularly for surgeons. The timing of percutaneous tracheostomy in critically ill patients, and the use of the technique in children remain controversial.

Treatment of compulsive behaviour in eating disorders with intermittent ketamine infusions.

We have previously shown that eating disorders are a compulsive behaviour disease, characterized by frequent recall of anorexic thoughts. Evidence suggests that memory is a neocortical neuronal network, excitation of which involves the hippocampus, with recall occurring by re-excitement of the same specific network. Excitement of the hippocampus by glutamate-NMDA receptors, leading to long-term potentiation (LTP), can be blocked by ketamine. Continuous block of LTP prevents new memory formation but does not affect previous memories. Opioid antagonists prevent loss of consciousness with ketamine but do not prevent the block of LTP. We used infusions of 20 mg per hour ketamine for 10 h with 20 mg twice daily nalmefene as opioid antagonist to treat 15 patients with a long history of eating disorder, all of whom were chronic and resistant to several other forms of treatment. Nine (responders) showed prolonged remission when treated with two to nine ketamine infusions at intervals of 5 days to 3 weeks. Clinical response was associated with a significant decrease in Compulsion score: before ketamine, mean +/- SE was 44.0 +/- 2.5; after ketamine, 27.0 +/- 3.5 (t test, p = 0.0016). In six patients (non-responders) the score was: before ketamine, 42.8 +/- 3.7; after ketamine, 44.8 +/- 3.1. There was no significant response to at least five ketamine treatments, perhaps because the compulsive drive was re-established too soon after the infusion, or because the dose of opioid antagonist, nalmefene, was too low.

Reasons for withdrawing treatment in patients receiving intensive care.

We studied the frequency with which treatment was withdrawn in intensive care patients and the primary reason for reaching the decision. The medical records of patients having had active treatment withdrawn between August 1992 and February 1996 inclusive were reviewed. Patients were classified into an imminent death group consisting of those expected to die, a qualitative group who had treatment withdrawn on quality of life considerations and a lethal conditions group who had associated disease that precluded long-term survival. There were 1745 patients admitted, of whom 338 (19.4%) died in ICU. In 220 patients death followed the withdrawal of treatment (12.6% of all ICU admissions), 203 dying on ICU (60% of ICU deaths) and a further 17 soon after discharge to a ward. The primary reason for treatment withdrawal was imminent death in 45% of patients, qualitative considerations in 50% and lethal conditions in 5%. The reason varied significantly depending on the patient's age. Treatment is withdrawn commonly in ICU, the primary reason being quality of life considerations as often as because death is the expected outcome.