Adrian Mellor

Severe acute mountain sickness, brain natriuretic peptide and NT-proBNP in humans.

To examine the response of brain natriuretic peptide (BNP) and NT‐proBNP to high altitude (HA) both at rest and following exercise.

Anaesthesia In Austere Environments

The scope of this review is by necessity somewhat limited and, as said in the introduction, methods used will depend on the skills and experience of the practitioner involved. The triservice apparatus remains the system of choice for delivering volatile anaesthetic agents to patients in areas without the infrastructure to supply an endless quantity of medical gases, the planned isolated or battle conditions of Boultons scenarios. The TSAs portability, robust design and versatility have stood the test of time. By reviewing intravenous agents the author has attempted to find an evidence base for the most appropriate agent for a non anaesthetic trained doctor finding his or herself called on to provide emergency anaesthesia in the field. The most useful drug is ketamine which has the advantage of cardiovascular stability, preservation of airway reflexes, ease of administration via different routes and versatility for providing analgesia, sedation or general anaesthesia.

The effects of acute hypobaric hypoxia on arterial stiffness and endothelial function and its relationship to changes in pulmonary artery pressure and left ventricular diastolic function

This study investigated, for the first time, the effects of simulated high altitude, following acute hypobaric hypoxia (HH), on simultaneous assessment of large artery stiffness and endothelial function and its inter-relationship to left ventricular (LV) diastolic function, pulmonary artery systolic pressure (PASP), and estimated PA vascular resistance (PVR). Ten healthy subjects were studied at baseline pre and following acute HH to 4800u2009m for a total of 180 minutes. Assessments of LV diastolic function, mitral inflow, estimated LV filling pressure (E/e), PVR, and PASP were undertaken using transthoracic echocardiography. Simultaneous assessments of arterial stiffness index (SI), systemic vascular resistance (SVR), vascular tone, and endothelial function (reflective index [RI]) were performed using pulse contour analysis of the digital arterial waveform. Acute hypoxia led to a fall in SpO₂ (98.1±0.7 vs. 71.8±7.1%; p=0.0002), SVR (1589.1±191.2 vs. 1187.8±248.7; p=0.004), and RI (50.8±10.3 vs. 33.0±6.5%; p=0.0008) with an increase in PASP (24.3±2.2 to 35.0±5.3u2009mmHg; p=0.0001) and estimated PVR (116.40±19.0 vs. 144.6±21.5; p<0.001). There was no rise in either SI (p=0.13), mitral early annular early e filling velocity or E/e. There was a significant inverse correlation between SpO₂ and PASP (r=-0.77; p<0.0001), PVR (r=-0.57; p=0.008) and between the fall in SpO₂ and change (Δ) in RI (baseline vs. 150u2009min, r=-0.52; p<0.001). There was a modest inverse correlation between ΔRI (lower ΔRI=worsening endothelial function) and ΔPAP (r=-0.55; p=0.10) and a strong inverse correlation between ΔRI and ΔPVR (r=-0.89; p=0.0007). Acute hypobaric hypoxia does not significantly alter large artery stiffness or cause overt LV diastolic function. However, the degree of hypoxia influences both the systemic endothelial and pulmonary vascular responses. This noted association is intriguing and requires further investigation.

Wilderness medicine at high altitude: recent developments in the field.

Travel to high altitude is increasingly popular. With this comes an increased incidence of high-altitude illness and therefore an increased need to improve our strategies to prevent and accurately diagnose these. In this review, we provide a summary of recent advances of relevance to practitioners who may be advising travelers to altitude. Although the Lake Louise Score is now widely used as a diagnostic tool for acute mountain sickness (AMS), increasing evidence questions the validity of doing so, and of considering AMS as a single condition. Biomarkers, such as brain natriuretic peptide, are likely correlating with pulmonary artery systolic pressure, thus potential markers of the development of altitude illness. Established drug treatments include acetazolamide, nifedipine, and dexamethasone. Drugs with a potential to reduce the risk of developing AMS include nitrate supplements, propagators of nitric oxide, and supplemental iron. The role of exercise in the development of altitude illness remains hotly debated, and it appears that the intensity of exercise is more important than the exercise itself. Finally, despite copious studies demonstrating the value of preacclimatization in reducing the risk of altitude illness and improving performance, an optimal protocol to preacclimatize an individual remains elusive.

Effects of altitude exposure on brain natriuretic peptide in humans.

Acute mountain sickness (AMS) is common at high altitude (HA) and associated with a relative failure of the natriuresis and diuresis that occurs at HA. The role of Brain Natriuretic Peptide (BNP) in this context has not been thoroughly investigated. We aimed to clarify if BNP rises in response to exercise at HA and if so whether this is related to AMS. 32 healthy subjects had assessments of BNP, aldosterone and AMS scores [as assessed by the AMS-C score of the Environmental Symptom Questionnaire (ESQ) and Lake Louise questionnaire] made following exertion at sea-level (SL), 3,400, 4,300 and 5,150xa0m. Data were analysed in the 23 subjects who did not consume drugs known to affect acclimatization. BNP (pg/ml, meanxa0±xa0SEM) was significantly higher at 5,150xa0m versus the lower altitudes (pxa0<xa00.001 for all): 7.1xa0±xa01; 6.1xa0±xa00.3; 6.8xa0±xa00.9 and 17.7xa0±xa05.1 at sea-level; 3,400, 4,300 and 5,150xa0m. In those that showed a BNP response at 5,150xa0m (nxa0=xa019) versus those that did not demonstrate a BNP response (nxa0=xa04) there was a significant difference in Lake Louise (LL) AMS scores at 5,150xa0m on day 10 of the expedition (mean LL score 3.3 vs. 0.75, pxa0=xa00.034) and day 11 (mean LL score 3.3 vs. 0, pxa0=xa00.003). This is the first report to demonstrate a significant rise in BNP at HA. A BNP response at 5,150xa0m may be associated with a greater likelihood of suffering AMS.

Cardiac biomarkers at high altitude.

BACKGROUNDnClassically, biomarkers such as the natriuretic peptides (NPs) BNP/NT-proBNP are associated with the diagnosis of heart failure and hs-cTnT with acute coronary syndromes. NPs are also elevated in pulmonary hypertension. High pulmonary artery systolic pressure (PASP) is a key feature of high altitude pulmonary edema (HAPE), which may be difficult to diagnose in the field. We have previously demonstrated that NPs are associated with high PASP and the presence of acute mountain sickness (AMS) in a small cohort at HA. We aimed to investigate the utility of several common cardiac biomarkers in diagnosing high PASP and AMS.nnnMETHODSn48 participants were assessed post-trekking and at rest at three altitudes: 3833u2009m, 4450u2009m, and 5129u2009m. NPs, hs-cTnT and hsCRP, were quantified using immunoassays, PASP was measured by echocardiography, and AMS scores were recorded.nnnRESULTSnSignificant changes occurred with ascent in NPs, hs-cTnT, hsCRP (all p<0.001) and PASP (p=0.006). A high PASP (≥40u2009mm Hg) was associated with higher NPs, NT-proBNP: 137±195 vs. 71.8±68 (p=0.001); BNP 15.3±18.1 vs. 8.7±6.6 (p=0.001). NPs were significantly higher in those with AMS or severe AMS vs. those without (severe AMS: NT-proBNP: 161.2±264 vs. 76.4±82.5 (p=0.008)). The NPs correlated with hsCRP. cTnT increased with exercise at HA and was also higher in those with a high PASP (13.8±21 vs. 7.8±6.5, p=0.018).nnnCONCLUSIONnThe NPs and hs-cTnT are associated with high PASP at HA and the NPs with AMS.

Anaesthetic and critical care management of thoracic injuries.

Thoracic wounding has been a relatively common presentation of military wounds throughout modern conflict. When civilian casualties are included the incidence has remained constant at around 10%, although the frequency and severity of wounds to combatants has been altered by modern body armour. Whilst thoracic injury has a high initial mortality on the battlefield, those surviving to reach hospital frequently have injuries that only require simple management. In addition to penetrating ballistic injury, blunt chest trauma frequently occurs on operations as a result of road traffic collisions or tertiary blast injury. The physiological impact of thoracic wounds, however, is often great and survivors often require intensive care management and, where available, complex strategies to ensure oxygenation and carbon dioxide removal. This review examines the incidence and patterns of thoracic trauma and looks at therapeutic options for managing these complex cases.

A Four-Way Comparison of Cardiac Function with Normobaric Normoxia, Normobaric Hypoxia, Hypobaric Hypoxia and Genuine High Altitude

Background There has been considerable debate as to whether different modalities of simulated hypoxia induce similar cardiac responses. Materials and Methods This was a prospective observational study of 14 healthy subjects aged 22–35 years. Echocardiography was performed at rest and at 15 and 120 minutes following two hours exercise under normobaric normoxia (NN) and under similar PiO2 following genuine high altitude (GHA) at 3,375m, normobaric hypoxia (NH) and hypobaric hypoxia (HH) to simulate the equivalent hypoxic stimulus to GHA. Results All 14 subjects completed the experiment at GHA, 11 at NN, 12 under NH, and 6 under HH. The four groups were similar in age, sex and baseline demographics. At baseline rest right ventricular (RV) systolic pressure (RVSP, p = 0.0002), pulmonary vascular resistance (p = 0.0002) and acute mountain sickness (AMS) scores were higher and the SpO2 lower (p<0.0001) among all three hypoxic groups (GHA, NH and HH) compared with NN. At both 15 minutes and 120 minutes post exercise, AMS scores, Cardiac output, septal S’, lateral S’, tricuspid S’ and A’ velocities and RVSP were higher and SpO2 lower with all forms of hypoxia compared with NN. On post-test analysis, among the three hypoxia groups, SpO2 was lower at baseline and 15 minutes post exercise with GHA (89.3±3.4% and 89.3±2.2%) and HH (89.0±3.1 and (89.8±5.0) compared with NH (92.9±1.7 and 93.6±2.5%). The RV Myocardial Performance (Tei) Index and RVSP were significantly higher with HH than NH at 15 and 120 minutes post exercise respectively and tricuspid A’ was higher with GHA compared with NH at 15 minutes post exercise. Conclusions GHA, NH and HH produce similar cardiac adaptations over short duration rest despite lower SpO2 levels with GHA and HH compared with NH. Notable differences emerge following exercise in SpO2, RVSP and RV cardiac function.

Serum neutrophil gelatinase-associated lipocalin in ballistic injuries: A comparison between blast injuries and gunshot wounds

UNLABELLEDnNeutrophil gelatinase-associated lipocalin (NGAL) is part of a functionally diverse family of proteins that generally bind small, hydrophobic ligands. Neutrophil gelatinase-associated lipocalin is expressed in a number of human tissues including gastrointestinal, respiratory, and urinary tracts and tends to rise in response to inflammation. For this reason, we hypothesized that levels of NGAL might be expressed at higher levels after blast injury compared with other ballistic injury.nnnPURPOSEnThe purpose of this study is to test the hypothesis that NGAL may be a marker of injury severity in blast injury.nnnMATERIALSnTwenty-three combat casualties (13 blast, 10 gunshot wounds) admitted to the multinational role 3 facility in Helmand province were studied. Serum NGAL was measured using a Biosite Triage point-of-care monitor at 5 time points after injury.nnnRESULTSnNeutrophil gelatinase-associated lipocalin rose in both groups of casualties and was significantly predictive of death or renal failure at intensive care unit admission, 12 and 24 hours after injury.nnnCONCLUSIONSnNeutrophil gelatinase-associated lipocalin is not a specific marker of blast injury but is predictive of both renal failure and poor outcome.

Haematological Changes at Altitude

Hypobaric hypoxia is associated with an increase in erythropoesis and an increased thrombotic risk. This is true of long haul air travel, mountaineering expeditions and longer stays at altitude. Studies looking at clotting on mountaineering expeditions are further complicated by the effects of exercise, plasma volume changes and the catecholamine response to hypoxia. This review examines the evidence for changes in clotting factors and functional clotting at altitude and considers the implications of altitude travel for those with pre-existing medical conditions.