IMPORTANCEIn patients who require mechanical ventilation for acute hypoxemic respiratory failure, further reduction in tidal volumes, compared with conventional low tidal volume ventilation, may improve outcomes. OBJECTIVE To determine whether lower tidal volume mechanical ventilation using extracorporeal carbon dioxide removal improves outcomes in patients with acute hypoxemic respiratory failure. DESIGN, SETTING, AND PARTICIPANTS This multicenter, randomized, allocation-concealed, open-label, pragmatic clinical trial enrolled 412 adult patients receiving mechanical ventilation for acute hypoxemic respiratory failure, of a planned sample size of 1120, between May 2016 and December 2019 from 51 intensive care units in the UK. Follow-up ended on March 11, 2020. INTERVENTIONS Participants were randomized to receive lower tidal volume ventilation facilitated by extracorporeal carbon dioxide removal for at least 48 hours (n = 202) or standard care with conventional low tidal volume ventilation (n = 210). MAIN OUTCOMES AND MEASURESThe primary outcome was all-cause mortality 90 days after randomization. Prespecified secondary outcomes included ventilator-free days at day 28 and adverse event rates. RESULTS Among 412 patients who were randomized (mean age, 59 years; 143 [35%] women), 405 (98%) completed the trial. The trial was stopped early because of futility and feasibility following recommendations from the data monitoring and ethics committee. The 90-day mortality rate was 41.5% in the lower tidal volume ventilation with extracorporeal carbon dioxide removal group vs 39.5% in the standard care group (risk ratio, 1.05 [95% CI, 0.83-1.33]; difference, 2.0% [95% CI, −7.6% to 11.5%]; P = .68). There were significantly fewer mean ventilator-free days in the extracorporeal carbon dioxide removal group compared with the standard care group (7.1 [95% CI, 5.9-8.3] vs 9.2 [95% CI, 7.9-10.4] days; mean difference, −2.1 [95% CI, −3.8 to −0.3]; P = .02). Serious adverse events were reported for 62 patients (31%) in the extracorporeal carbon dioxide removal group and 18 (9%) in the standard care group, including intracranial hemorrhage in 9 patients (4.5%) vs 0 (0%) and bleeding at other sites in 6 (3.0%) vs 1 (0.5%) in the extracorporeal carbon dioxide removal group vs the control group. Overall, 21 patients experienced 22 serious adverse events related to the study device.CONCLUSIONS AND RELEVANCE Among patients with acute hypoxemic respiratory failure, the use of extracorporeal carbon dioxide removal to facilitate lower tidal volume mechanical ventilation, compared with conventional low tidal volume mechanical ventilation, did not significantly reduce 90-day mortality. However, due to early termination, the study may have been underpowered to detect a clinically important difference.

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Visual field assessment is an important clinical evaluation for eye disease and neurological injury. We evaluated Octopus semi-automated kinetic peripheral perimetry (SKP) and Humphrey static automated central perimetry for detection of neurological visual field loss in patients with pituitary disease. We carried out a prospective cross-sectional diagnostic accuracy study comparing Humphrey central 30-2 SITA threshold programme with a screening protocol for SKP on Octopus perimetry. Humphrey 24-2 data were extracted from 30-2 results. Results were independently graded for presence/absence of field defect plus severity of defect. Fifty patients (100 eyes) were recruited (25 males and 25 females), with mean age of 52.4 years (SD = 15.7). Order of perimeter assessment (Humphrey/Octopus first) and order of eye tested (right/left first) were randomised. The 30-2 programme detected visual field loss in 85%, the 24-2 programme in 80%, and the Octopus combined kinetic/ static strategy in 100% of eyes. Peripheral visual field loss was missed by central threshold assessment. Qualitative comparison of type of visual field defect demonstrated a match between Humphrey and Octopus results in 58%, with a match for severity of defect in 50%. Tests duration was 9.34 minutes (SD = 2.02) for Humphrey 30-2 versus 10.79 minutes (SD = 4.06) for Octopus perimetry. Octopus semi-automated kinetic perimetry was found to be superior to central static testing for detection of pituitary disease-related visual field loss. Where reliant on Humphrey central static perimetry, the 30-2 programme is recommended over the 24-2 programme. Where kinetic perimetry is available, this is preferable to central static programmes for increased detection of peripheral visual field loss.

Most patients have had the classic bursts of smallamplitude, high-frequency rotary oscillations causing oscillopsia, defined as intermittent uniocular microtremor [8}. Others, however, have had a slower, larger-amplitude intorsional movement causing vertical and torsional diplopia. We have termed this movement macrorota y deviation (MRD). MRD has occurred most often in association with the more classic IUM C6-8, 10, 111, but in a few patients it has been the only or predominant eye movement abnormality C2, 7, 121. Other associated motility problems have included intermittent overaction of the ipsilateral superior oblique muscle 110-121, ipsilateral superior oblique paresis ( 7 , 101, and, in our patient, an intermittent Brown's syndrome.We suspect that all of the grossly visible movements (MRD, intermittent overaction of the superior oblique, and intermittent superior oblique tendon sheath syndrome) represent the same rotary entasia expressed differently when assessed by varying techniques. An alternate-cover test would reveal an overaction of the superior oblique muscle; an apparent Brown's syndrome would be diagnosed if the motor anomaly occurred during attempted gaze inward and upward; and the MRD itself would be observed only during direct observation.The cause of IUM and MRD is unclear. Their frequent concurrence implies a continuum of motor anomalies. Electromyographs of the two types of movements are similar, with evidence of chronic denervation, supporting the idea that both are manifestations of superior oblique myokymia [7, 91. Kommerell's patient with MRD had a more stable rate of firing than others with IUM, suggesting that the firing pattern of the abnormal motor units may determine the clinical picture E91. All electromyographic evidence to date supports Hoyt's original suggestion that SOM is primarily a nuclear disorder C7-91.Possibly pertinent to SOM is a report by Baker and Bertoz, who evaluated oblique nystagmus induced by vestibular lesions in alert "encephale isole" cats C11.Using intra-and extracellular recordings from inferior and superior oblique motor neurons, they noted a "rhythmic oscillation" in the electrical discharge from the oblique motor neurons immediately after a sudden decrease in the stimulation rate. The occurrence of such a "rhythmic oscillation" immediately after a sudden decrease in the stimulation rate could be the physiological basis for the clinical observation that the uniocular microtremor is most easily provoked by moving the eye into and then out of the field of action of the superior oblique muscle.The authors wish to thank Dr J. Lawton Smith for referring his patients to us for follow-up.