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.

IntroductionSeveral observational studies suggest that statins modulate the pathophysiology of sepsis and may prevent its progression. The aim of this study was to determine if the acute administration of atorvastatin reduces sepsis progression in statin naïve patients hospitalized with sepsis.MethodsA single centre phase II randomized double-blind placebo-controlled trial. Patients with sepsis were randomized to atorvastatin 40 mg daily or placebo for the duration of their hospital stay up to a maximum of 28-days. The primary end-point was the rate of sepsis progressing to severe sepsis during hospitalization.Results100 patients were randomized, 49 to the treatment with atorvastatin and 51 to placebo. Patients in the atorvastatin group had a significantly lower conversion rate to severe sepsis compared to placebo (4% vs. 24% p = 0.007.), with a number needed to treat of 5. No significant difference in length of hospital stay, critical care unit admissions, 28-day and 12-month readmissions or mortality was observed. Plasma cholesterol and albumin creatinine ratios were significantly lower at day 4 in the atorvastatin group (p < 0.0001 and p = 0.049 respectively). No difference in adverse events between the two groups was observed (p = 0.238).ConclusionsAcute administration of atorvastatin in patients with sepsis may prevent sepsis progression. Further multi-centre trials are required to verify these findings.Trial RegistrationInternational Standard Randomized Control Trial Registry ISRCTN64637517.

Severe sepsis and septic shock is common and frequently fatal. Over the last few years, the primary treatments demonstrated to improve outcome from several major clinical trials have finally emerged. However, translating these recent therapeutic advances to routine clinical practice has proven controversial, and new approaches of additional strategies are continued to be developed. Given their pleiotropic effects related to many pathophysiological determinants of sepsis, statin therapy could be the next step in the search for adjuvant therapy. A future challenge may be to test both the efficacy and the safety by large randomized controlled clinical trials ascertaining the effects of statins administered at the onset of sepsis and in patients with severe sepsis or septic shock admitted into intensive care units.

A 65-year-old man underwent parathyroidectomy for hyperparathyroidism secondary to renal failure. Intra-operatively he received methylene blue infusion (7.5 mg.kg )1 , a total of 650 mg in 500 ml 0.9% sodium chloride) for visualisation of parathyroid glands. At the end of surgery, following extubation he developed agitation, intense shivering and hyperpyrexia, and his level of consciousness decreased to a Glasgow Coma score of 7. The differential diagnoses included methylene blue toxicity or malignant hyperpyrexia. His lungs were ventilated, and intravenous dantrolene was administered to control hyperpyrexia. Haemodialysis was started to remove the methylene blue dye. We review the literature on the pharmacological actions of methylene blue, and discuss the differential diagnosis and management of this patient. Parathyroidectomy is frequently performed for primary hyperparathyroidism due to a single adenoma, secondary hyperparathyroidism due to hypocalcaemia, typically associated with chronic renal failure, or tertiary hyperparathyroidism when an overacting parathyroid gland becomes autonomous. It is essential to remove all four parathyroid glands effectively to control the symptoms of secondary hyperparathyroidism. Intravenous methylene blue has often been used to aid in the visualisation of the parathyroid glands, as the dye is preferentially sequestered in them. Although considered to be relatively innocuous, methylene blue administration has been associated with complications. It is thought to cause nausea, abdominal and chest pain, headache, dizziness, mental confusion, profuse sweating and hypertension [1]. We describe a case of prolonged confusion and hyperpyrexia following methylene blue infusion during parathyroidectomy. Case reportA 65-year-old male with dialysis dependent end stage renal failure underwent parathyroidectomy for secondary hyperparathyroidism. His past medical history included type II diabetes mellitus, systemic hypertension and ischaemic heart disease. His parathormone level (PTH) was 907 ng.l )1 (normal levels 10-55 pg ml )1 ) and corrected calcium levels ranged between 2.61-2.72 mmol.l )1 . His medication included insulin, quinine sulphate, omeprazole, clopidogrel, atorvastatin, alfacalcidol, citalopram, aluminium hydroxide and sildenafil. He had no known drug allergies. He had recently undergone an uneventful general anaesthetic involving the administration of a volatile agent for amputation of a toe. He received dialysis on the day prior to surgery and his post dialysis blood results were deemed satisfactory. The patient was started on a methylene blue infusion at a dose of 7.5 mg.kg )1 (650 mg methylene blue in 500 ml 0.9% NaCl) just before his arrival in the operating theatre. The infusion had to be discontinued in the anaesthetic room since he had become distressed and started vomiting. General anaesthesia was induced using propofol 2.5 mg.kg , fentanyl 1.5 lg.kg )1 and his trachea was intubated following neuromuscular blockade using atracurium 0.6 mg.kg )1. Anaesthesia was maint...

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Chlorhexidine (CHX) and octenidine (OCT), antimicrobial compounds used in oral care products (toothpastes and mouthwashes), were recently revealed to interfere with human sex hormone receptor pathways. Experiments employing model organisms—white-rot fungi Irpex lacteus and Pleurotus ostreatus—were carried out in order to investigate the biodegradability of these endocrine-disrupting compounds and the capability of the fungi and their extracellular enzyme apparatuses to biodegrade CHX and OCT. Up to 70% ± 6% of CHX was eliminated in comparison with a heat-killed control after 21 days of in vivo incubation. An additional in vitro experiment confirmed manganese-dependent peroxidase and laccase are partially responsible for the removal of CHX. Up to 48% ± 7% of OCT was removed in the same in vivo experiment, but the strong sorption of OCT on fungal biomass prevented a clear evaluation of the involvement of the fungi or extracellular enzymes. On the other hand, metabolites indicating the enzymatic transformation of both CHX and OCT were detected and their chemical structures were proposed by means of liquid chromatography–mass spectrometry. Complete biodegradation by the ligninolytic fungi was not achieved for any of the studied analytes, which emphasizes their recalcitrant character with low possibility to be removed from the environment.