Methoxyflurane for Procedural Analgesia at 4470 m Altitude.

Methoxyflurane is a volatile, fluorinated anesthetic agent with analgesic properties. Although no longer used as an anesthetic due to concerns regarding renal toxicity in high doses, it has enjoyed a resurgence as an inhaled analgesic in prehospital care and in the emergency department. The agent is nonflammable and leads to rapid, titratable analgesia without intravenous access. The Penthrox inhaler device is light, robust, and straightforward to administer. Consequently, it has been proposed as an ideal analgesic for the remote high altitude setting. We report its use for procedural analgesia during suprapubic aspiration for acute urinary retention at a remote rescue post at night, in cold winter conditions, at 4470 m altitude in Machermo, Nepal. We found that methoxyflurane provided rapid, effective analgesia for our patient's visceral and procedural pain. The inhaler was easy to administer, and the patient remained responsive to voice, with satisfactory oxygen saturation and respiratory rate throughout. We also briefly review the administration, dosing, efficacy, and safety of methoxyflurane and its role in remote medical care.

Changes in plasma bradykinin concentration and citric acid cough threshold at high altitude.

OBJECTIVE: Altitude-related cough is a troublesome condition of unknown etiology. Inhaled tussive agents are used to quantify cough, and the citric acid cough threshold has been shown to fall on ascent to altitude. Cough can occur in patients taking angiotensin-converting enzyme inhibitors due to stimulation of airway sensory receptors by increased levels of bradykinin. We hypothesized that increased levels of bradykinin could be responsible for the decrease in citric acid cough threshold on exposure to altitude and a possible etiologic factor in altitude-related cough. METHODS: Twenty healthy volunteers underwent baseline tests at 700 m before a 2-week stay at 3800 m. Angiotensin-converting enzyme activity and plasma bradykinin were measured at baseline and altitude. Citric acid cough threshold and nocturnal cough frequency were measured at baseline and throughout the 2 weeks at altitude. RESULTS: Citric acid cough threshold fell from 3.7 g/dL at baseline to 2.1 g/dL on the second day at 3800 m (geometric mean difference 1.8, 95% CIs 1.0-5.0, P = .025) and remained reduced throughout the stay at altitude. Nocturnal cough frequency was unchanged compared to baseline. Plasma bradykinin fell from 0.43 ng/mL at baseline to 0.08 ng/mL at altitude (geometric mean difference 5.7, 95% CIs 2.1-15.5, P = .002), but angiotensin-converting enzyme activity was unchanged (mean difference 0.06, 95% CIs -2.7-2.8, P = .97). There was no correlation between plasma bradykinin and citric acid cough threshold. CONCLUSIONS: Increased levels of bradykinin are unlikely to be a significant factor in the increased sensitivity to citric acid seen in hypobaric hypoxia. Further studies are required to elucidate the etiology of altitude-related cough.

Overnight duty impairs behaviour, awake activity and sleep in medical doctors.

BACKGROUND: The impact of prolonged work cycles among senior doctors remains disputed. We evaluated the effects of overnight duty on awake activity and sleep quality in senior doctors in emergency medical specialties. METHODS: Thirty-six healthy doctors were monitored during a 2-week period including three separate 84 h on-call cycles. An on-call cycle consisted of the night and the day before night duty; the night duty itself and the subsequent 2 days and nights after night duty. The first day after night duty could either be worked or not. Actigraphy was used to measure physical activity and to evaluate sleep duration and quality. A standardized questionnaire was used to assess daytime performance and night sleep quality. RESULTS: Night actigraphy demonstrated that on-call work induced a significant reduction in sleep duration that was not recovered during the subsequent two nights. Sleep during the night duty itself was fragmented and of poor quality. Awake activity was significantly impaired on the day after night duty. Although subjectively night sleep quality did not differ between the nights before and after night duty, all subjective daytime parameters were impaired the day after night duty, and mood, fatigue and concentration remained altered on the second day. Working the day after night duty impaired objective measurements of daytime activity and sleep quality during the subsequent two nights. CONCLUSIONS: On-call night work in acute specialties induces sleep debt associated with prolonged impairment of awake activity, sleep quality and performance. Not working the following day after an on-call night allows partial recovery of sleep quality to begin.

Serial changes in nasal potential difference and lung electrical impedance tomography at high altitude.

Recent work suggests that treatment with inhaled beta(2)-agonists reduces the incidence of high-altitude pulmonary edema in susceptible subjects by increasing respiratory epithelial sodium transport. We estimated respiratory epithelial ion transport by transepithelial nasal potential difference (NPD) measurements in 20 normal male subjects before, during, and after a stay at 3,800 m. NPD hyperpolarized on ascent to 3,800 m (P < 0.05), but the change in potential difference with superperfusion of amiloride or isoprenaline was unaffected. Vital capacity (VC) fell on ascent to 3,800 m (P < 0.05), as did the normalized change in electrical impedance (NCI) measured over the right lung parenchyma (P < 0.05) suggestive of an increase in extravascular lung water. Echo-Doppler-estimated pulmonary artery pressure increases were insufficient to cause clinical pulmonary edema. There was a positive correlation between VC and NCI (R(2) = 0.633) and between NPD and both VC and NCI (R(2) = 0.267 and 0.418). These changes suggest that altered respiratory epithelial ion transport might play a role in the development of subclinical pulmonary edema at high altitude in normal subjects.

Altitude-related cough.

Altitude-related cough is a troublesome condition of uncertain aetiology that affects many visitors to high altitude. The traditionally held belief that it was due solely to the inspiration of cold, dry air was refuted by observations and experiments in long duration hypobaric chamber studies. It is likely that altitude-related cough is a symptom of a number of possible perturbations in the cough reflex arc that may exist independently or together. These include loss of water from the respiratory tract; respiratory tract infections and sub-clinical high altitude pulmonary oedema. The published work on altitude-related cough is reviewed and possible aetiologies for the condition are discussed.

The citric acid cough threshold and the ventilatory response to carbon dioxide on ascent to high altitude.

Ventilatory control undergoes profound changes on ascent to high altitude. We hypothesized that the fall in citric acid cough threshold seen on ascent to altitude is mediated by changes in the central control of cough and would parallel changes in central ventilatory control assessed by the hypercapnic ventilatory response (HCVR). Twenty-five healthy volunteers underwent measurements of HCVR and citric acid sensitivity at sea level and during a 9 day sojourn at 5200m. None of the subjects had any evidence of respiratory infection. Citric acid cough threshold fell significantly on ascent to 5200m. The slope, S, of the HCVR increased significantly on ascent to 5200m and during the stay at altitude. There was no correlation between citric acid sensitivity and HCVR. We conclude that the change in citric acid cough threshold seen on exposure to hypobaric hypoxia is unlikely to be mediated by changes in the central control of cough. Sensitivity to citric acid may be due to early subclinical pulmonary edema stimulating airway sensory nerve endings.

Altitude-related cough.

Cough is a troublesome condition which affects many visitors to high altitude. Traditionally it has been attributed to the inspiration of the cold, dry air which characterizes the high altitude environment. This aetiology was brought into question by observations and experiments in long duration hypobaric chamber studies in which cough still occurred despite controlled temperature and humidity. Anecdotally however, exercise, possibly via the associated increase in ventilation, does appear to precipitate cough at altitude. It is likely that the term, altitude-related cough, covers a number of conditions and aetiologies. These aetiologies are discussed and include water loss from the respiratory tract; high altitude pulmonary oedema; acute mountain sickness; bronchoconstriction; respiratory tract infections; vasomotor rhinitis and post-nasal drip; and alterations in the central control of respiration. We hypothesize that there are two forms of altitude-related cough: a cough which may occur at relatively low altitudes and which is related to exercise and persists despite descent and a cough which does not occur at altitudes below 5000-6000 m and which improves rapidly with descent to lower altitude. The treatment of altitude-related cough is symptomatic and frequently ineffective. Further work is required to understand the nature and aetiology of the cough which occurs at high altitude before effective therapies can be developed.