C. Imray

Cerebral artery dilatation maintains cerebral oxygenation at extreme altitude and in acute hypoxia—an ultrasound and MRI study

Transcranial Doppler is a widely used noninvasive technique for assessing cerebral artery blood flow. All previous high altitude studies assessing cerebral blood flow (CBF) in the field that have used Doppler to measure arterial blood velocity have assumed vessel diameter to not alter. Here, we report two studies that demonstrate this is not the case. First, we report the highest recorded study of CBF (7,950 m on Everest) and demonstrate that above 5,300 m, middle cerebral artery (MCA) diameter increases (n = 24 at 5,300 m, 14 at 6,400 m, and 5 at 7,950 m). Mean MCA diameter at sea level was 5.30 mm, at 5,300 m was 5.23 mm, at 6,400 m was 6.66 mm, and at 7,950 m was 9.34 mm (P<0.001 for change between 5,300 and 7,950 m). The dilatation at 7,950 m reversed with oxygen. Second, we confirm this dilatation by demonstrating the same effect (and correlating it with ultrasound) during hypoxia (FiO2 = 12% for 3 hours) in a 3-T magnetic resonance imaging study at sea level (n = 7). From these results, we conclude that it cannot be assumed that cerebral artery diameter is constant, especially during alterations of inspired oxygen partial pressure, and that transcranial 2D ultrasound is a technique that can be used at the bedside or in the remote setting to assess MCA caliber.

Mortality on Mount Everest, 1921-2006: descriptive study

Objective To examine patterns of mortality among climbers on Mount Everest over an 86 year period. Design Descriptive study. Setting Climbing expeditions to Mount Everest, 1921-2006. Participants 14 138 mountaineers; 8030 climbers and 6108 sherpas. Main outcome measure Circumstances of deaths. Results The mortality rate among mountaineers above base camp was 1.3%. Deaths could be classified as involving trauma (objective hazards or falls, n=113), as non-traumatic (high altitude illness, hypothermia, or sudden death, n=52), or as a disappearance (body never found, n=27). During the spring climbing seasons from 1982 to 2006, 82.3% of deaths of climbers occurred during an attempt at reaching the summit. The death rate during all descents via standard routes was higher for climbers than for sherpas (2.7% (43/1585) v 0.4% (5/1231), P<0.001; all mountaineers 1.9%). Of 94 mountaineers who died after climbing above 8000 m, 53 (56%) died during descent from the summit, 16 (17%) after turning back, 9 (10%) during the ascent, 4 (5%) before leaving the final camp, and for 12 (13%) the stage of the summit bid was unknown. The median time to reach the summit via standard routes was earlier for survivors than for non-survivors (0900-0959 v 1300-1359, P<0.001). Profound fatigue (n=34), cognitive changes (n=21), and ataxia (n=12) were the commonest symptoms reported in non-survivors, whereas respiratory distress (n=5), headache (n=0), and nausea or vomiting (n=3) were rarely described. Conclusions Debilitating symptoms consistent with high altitude cerebral oedema commonly present during descent from the summit of Mount Everest. Profound fatigue and late times in reaching the summit are early features associated with subsequent death.

Blood levels of donor-specific human leukocyte antigen antibodies after renal transplantation : Resolution of rejection in the presence of circulating donor-specific antibody

Background. Accommodation to antibody is an important mechanism in successful ABO-incompatible transplantation, but its importance in human leukocyte antigen (HLA) antibody-incompatible transplantation is less clear, as sensitive techniques facilitating daily measurement of donor-specific HLA antibodies (DSAs) have only recently been developed. Methods. We report 24 patients who had HLA antibody-incompatible kidney transplantation (21 living donors, 3 deceased), 21 of whom had pretransplant plasmapheresis. Eight had positive complement-dependent cytotoxic (CDC) crossmatch (XM) pretransplant plasmapheresis, nine had positive flow cytometric (FC) XM, and seven had DSA detectable by microbead analysis only. After transplant, DSA levels were monitored closely with microbead assays. Results. Rejection occurred in five of eight (62.5%) CDC-positive cases, in three of nine (33%) FC-positive cases, and in two of seven (29%) of microbead-only cases at a median of 6.5 days after transplantation. Resolution occurred at a median of 15 days after transplantation, in 8 of 10 cases when the microbead level of DSA had median fluorescence intensity (MFI) >2000 U, in 6 of 10 when the microbead MFI >4000 U. In 8 of 10 cases, the microbead MFI at the time of resolution was greater than at the onset. DSA did not always cause clinical rejection. In five cases with a posttransplant DSA peaking at MFI >2000 U on microbead assay, rejection did not occur. Conclusion. These data suggest that the dominant method of successful transplantation was function of the transplant in the presence of circulating DSA, and they also define the period during which this occurred.

Human leukocyte antigen antibody-incompatible renal transplantation: excellent medium-term outcomes with negative cytotoxic crossmatch.

Background. Human leukocyte antigen (HLA) antibody-incompatible renal transplantation has been increasingly performed since 2000 but with few data on the medium-term outcomes. Methods. Between 2003 and 2011, 84 patients received renal transplants with a pretreatment donor-specific antibody (DSA) level of more than 500 in a microbead assay. Seventeen patients had positive complement-dependent cytotoxic (CDC) crossmatch (XM), 44 had negative CDC XM and positive flow cytometric XM, and 23 had DSA detectable by microbead only. We also reviewed 28 patients with HLA antibodies but no DSA at transplant. DSAs were removed with plasmapheresis pretransplant, and patients did not routinely receive antithymocyte globulin posttransplant. Results. Mean follow-up posttransplantation was 39.6 (range 2–91) months. Patient survival after the first year was 93.8%. Death-censored graft survival at 1, 3, and 5 years was 97.5%, 94.2%, and 80.4%, respectively, in all DSA+ve patients, worse at 5 years in the CDC+ve than in the CDC−ve/DSA+ve group at 45.6% and 88.6%, respectively (P<0.03). Five-year graft survival in the DSA−ve group was 82.1%. Rejection occurred in 53.1% of DSA+ve patients in the first year compared with 22% in the DSA−ve patients (P<0.003). Conclusions. HLA antibody-incompatible renal transplantation had a high success rate if the CDC XM was negative. Further work is required to predict which CDC+ve XM grafts will be successful and to treat slowly progressive graft damage because of DSA in the first few years after transplantation.

The role of feedback in improving the effectiveness of workplace based assessments: a systematic review

BackgroundWith recent emphasis placed on workplace based assessment (WBA) as a method of formative performance assessment, there is limited evidence in the current literature regarding the role of feedback in improving the effectiveness of WBA. The aim of this systematic review was to elucidate the impact of feedback on the effectiveness of WBA in postgraduate medical training.MethodsSearches were conducted using the following bibliographic databases to identify original published studies related to WBA and the role of feedback: Medline (1950-December 2010), Embase (1980-December 2010) and Journals@Ovid (English language only, 1996-December 2010). Studies which attempted to evaluate the role of feedback in WBA involving postgraduate doctors were included.Results15 identified studies met the inclusion criteria and minimum quality threshold. They were heterogeneous in methodological design. 7 studies focused on multi source feedback, 3 studies were based on mini-clinical evaluation exercise, 2 looked at procedural based assessment, one study looked at workplace based assessments in general and 2 studies looked at a combination of 3 to 6 workplace based assessments. 7 studies originated from the United Kingdom. Others were from Canada, the United States and New Zealand. Study populations were doctors in various grades of training from a wide range of specialties including general practice, general medicine, general surgery, dermatology, paediatrics and anaesthetics. All studies were prospective in design, and non-comparative descriptive or observational studies using a variety of methods including questionnaires, one to one interviews and focus groups.ConclusionsThe evidence base contains few high quality conclusive studies and more studies are required to provide further evidence for the effect of feedback from workplace based assessment on subsequent performance. There is, however, good evidence that if well implemented, feedback from workplace based assessments, particularly multisource feedback, leads to a perceived positive effect on practice.

Wilderness Medical Society Practice Guidelines for the Prevention and Treatment of Frostbite

The Wilderness Medical Society convened an expert panel to develop a set of evidence-based guidelines for the prevention and treatment of frostbite. We present a review of pertinent pathophysiology. We then discuss primary and secondary prevention measures and therapeutic management. Recommendations are made regarding each treatment and its role in management. These recommendations are graded based on the quality of supporting evidence and balance between the benefits and risks/burdens for each modality according to methodology stipulated by the American College of Chest Physicians.

The headache of high altitude and microgravity—similarities with clinical syndromes of cerebral venous hypertension

Syndromes thought to have cerebral venous hypertension as their core, such as idiopathic intracranial hypertension and jugular foramen outlet obstruction, classically result in headaches. Do they provide an insight into the cause of the headache that commonly occurs at altitude? The classic theory of the pathogenesis of high altitude headache has been that it results from increased intracranial pressure (ICP) secondary to hypoxemia in people who have less compliant intracranial volumes (Roach and Hackett, 2001). However, there does not appear to be a correlation between the headache of acute mountain sickness (AMS) and the presence of cerebral edema (Bailey et al, 2006; Wilson et al, 2009). Research has concentrated on arterial perfusion to the brain in hypoxia, but there has been little study of venous drainage. Hypoxia results in markedly increased cerebral blood flow; however, if it has been considered at all, venous outflow has to date been assumed to be of little consequence. Retinal venous distension and the increased venous blood demonstrated by near infra-red spectroscopy and more recently by MRI imply that, in hypoxia, a relative venous insufficiency may exist. Similarly, there is increasing evidence that manifestations of the fluid shift during microgravity is of similar nature to idiopathic intracranial hypertension, which is thought to be primarily a venous insufficiency condition. The unique anthropomorphic adaptations of large brained biped humans with cerebral venous systems that have to cope with large changes in hydrostatic pressure may predispose us to conditions of inflow/outflow mismatch. In addition, slight increases in central venous pressures (e.g., from hypoxia-induced pulmonary vasoconstriction) may further compromise venous outflow at altitude. A better understanding of cerebral venous physiology may enlighten us with regards the pathogenesis of headaches currently considered idiopathic. It may also enable us to trigger headaches for study and hence enable us to develop new treatment strategies.

Acute Kidney Injury After Endovascular Repair of Abdominal Aortic Aneurysm

Acute kidney injury (AKI) after any type of intervention negatively impacts mortality, length of hospitalization, and perhaps long-term survival. In the case of endovascular aneurysm repair (EVAR), the incidence of AKI ranges from 1% to 23% for elective and emergency procedures and is lower compared to open repair. The pathophysiology of AKI in EVAR is complex: contrast-induced nephropathy, renal microembolization, and acute tubular necrosis are all implicated. Prevention strategies include hydration, ischemic preconditioning, regional anesthesia, and pharmacological agents. There is no level I evidence regarding the prevention of AKI in EVAR, so this review sought to examine the mechanisms and prevention strategies for this potentially fatal complication.

Are some strokes preventable? The potential role of transcranial doppler in transient ischaemic attacks of carotid origin.

Transient ischaemic attacks (TIA) are more than just ministrokes. The high frequency of early stroke following TIA has resulted in the recent publication of guidelines in the UK. The guidelines recommend that patients attend a neurovascular clinic within 7 days of the index event to expedite investigation and treatment and so reduce the risk of a subsequent (potentially more serious) neurological event. After a TIA or stroke caused by carotid-artery disease, there is an increase in cerebral microemboli detectable by transcranial doppler (TCD). High microembolic loads appear to be surrogate markers for future neurological events, and the pharmacological efficacy of therapeutic interventions can now be rapidly and non-invasively assessed in the clinic or at the bedside. Medical treatments can now be optimised, avoiding the need for urgent or emergency carotid surgery and therefore allowing patients to undergo safer elective surgery when appropriate.

Control of emboli in patients with recurrent or crescendo transient ischaemic attacks using preoperative transcranial Doppler-directed Dextran therapy†

Transcranial Doppler (TCD)‐directed Dextran 40 treatment after carotid endarterectomy reduces the rate of early postoperative thrombosis. This study assessed the efficacy of intravenous Dextran 40 at controlling symptoms and emboli before elective carotid endarterectomy in patients with recurrent or crescendo transient ischaemic attacks (TIAs).