Effect of a Low vs Intermediate Tidal Volume Strategy on Ventilator-Free Days in Intensive Care Unit Patients Without ARDS: A Randomized Clinical Trial.

Importance: It remains uncertain whether invasive ventilation should use low tidal volumes in critically ill patients without acute respiratory distress syndrome (ARDS). Objective: To determine whether a low tidal volume ventilation strategy is more effective than an intermediate tidal volume strategy. Design, Setting, and Participants: A randomized clinical trial, conducted from September 1, 2014, through August 20, 2017, including patients without ARDS expected to not be extubated within 24 hours after start of ventilation from 6 intensive care units in the Netherlands. Interventions: Invasive ventilation using low tidal volumes (n = 477) or intermediate tidal volumes (n = 484). Main Outcomes and Measures: The primary outcome was the number of ventilator-free days and alive at day 28. Secondary outcomes included length of ICU and hospital stay; ICU, hospital, and 28- and 90-day mortality; and development of ARDS, pneumonia, severe atelectasis, or pneumothorax. Results: In total, 961 patients (65% male), with a median age of 68 years (interquartile range [IQR], 59-76), were enrolled. At day 28, 475 patients in the low tidal volume group had a median of 21 ventilator-free days (IQR, 0-26), and 480 patients in the intermediate tidal volume group had a median of 21 ventilator-free days (IQR, 0-26) (mean difference, -0.27 [95% CI, -1.74 to 1.19]; P = .71). There was no significant difference in ICU (median, 6 vs 6 days; 0.39 [-1.09 to 1.89]; P = .58) and hospital (median, 14 vs 15 days; -0.60 [-3.52 to 2.31]; P = .68) length of stay or 28-day (34.9% vs 32.1%; hazard ratio [HR], 1.12 [0.90 to 1.40]; P = .30) and 90-day (39.1% vs 37.8%; HR, 1.07 [0.87 to 1.31]; P = .54) mortality. There was no significant difference in the percentage of patients developing the following adverse events: ARDS (3.8% vs 5.0%; risk ratio [RR], 0.86 [0.59 to 1.24]; P = .38), pneumonia (4.2% vs 3.7%; RR, 1.07 [0.78 to 1.47]; P = .67), severe atelectasis (11.4% vs 11.2%; RR, 1.00 [0.81 to 1.23]; P = .94), and pneumothorax (1.8% vs 1.3%; RR, 1.16 [0.73 to 1.84]; P = .55). Conclusions and Relevance: In patients in the ICU without ARDS who were expected not to be extubated within 24 hours of randomization, a low tidal volume strategy did not result in a greater number of ventilator-free days than an intermediate tidal volume strategy. Trial Registration: ClinicalTrials.gov Identifier: NCT02153294.

[Allergy and anaphylaxis]. / Allergie en anafylaxie.

Allergy is a medical condition of frequent occurrence. In the Netherlands approximately 20% of the population has some kind of respiratory allergy, due to pollen and dust mites. The occurrence of allergy on foods, antibiotics, other medications, contrast fluid and insect poison is estimated to be 2% in the adult population. Because of this large and diverse group of allergy triggers it is very likely that physicians, regardless of background or medical specialty, will come across questions regarding allergy at some point in their career. The severity of an allergic reaction can vary, with anaphylaxis as one of the most severe and potentially life-threatening reactions (among DRESS, SJS, TEN and acute FPIES). This article describes the backgrounds of IgE-mediated allergy and anaphylaxis, like pathophysiology, diagnostics and treatment.

An 80-Year-Old Man With Respiratory Insufficiency After Intravesical Mycobacterium bovis BCG Immunotherapy.

CASE PRESENTATION: An 80-year-old man came to the ED with fever, hematuria, and overall discomfort for 1 week. His medical history included a superficial urothelial carcinoma of the bladder for which he was adjunctively treated with intravesical Mycobacterium bovis BCG (bacillus Calmette-Guérin) immunotherapy for several months. The patient was admitted to the hospital and was initially treated with cephalosporins for a suspected complicated urinary tract infection, but his symptoms did not improve. Ten days after the initial admission, the patient developed hypoxemic respiratory failure during an episode of fever and cold chills and was admitted to the ICU.

An observational, prospective, two-cohort comparison of a fixed versus variable dosing strategy of prothrombin complex concentrate to counteract vitamin K antagonists in 240 bleeding emergencies.

BACKGROUND: Despite years of experience with vitamin K antagonist-associated bleeding events, there is still no evidence to help identify the optimal treatment with prothrombin complex concentrates. Variable dosing and fixed dose strategies are being used. In this observational prospective two-cohort study, we aimed to assess the non-inferiority of a low fixed PCC dose (1,040 IU Factor IX) compared to the registered variable dosing regimen based on baseline International Normalized Rate, bodyweight, and target International Normalized Rate, to counteract vitamin K antagonists in a bleeding emergency in a daily clinical practice setting. DESIGN AND METHODS: Non-inferiority of the fixed prothrombin complex concentrate dose was hypothesized with a margin of 4%. Main end points were proportion of patients reaching the target International Normalized Rate (< 2.0) after prothrombin complex concentrate treatment, and successful clinical outcome. RESULTS: Target International Normalized Rate was reached in 92% of the fixed dose patients (n=101) versus 95% of variable dose patients (n=139) resulting in a risk difference of -2.99% (90% CI: - 8.6 to 2.7) (non-inferiority not confirmed). Clinical outcome was successful in 96% and 88% of fixed versus variable dose, respectively, with a risk difference of 8.3% (90% CI: 2.7-13.9; non-inferiority confirmed). CONCLUSIONS: Although a lower fixed prothrombin complex concentrate dose was associated with successful clinical outcome, fewer patients reached the target International Normalized Rate.

[Neurotropic disease after vaccination against yellow fever]. / Neurotropische ziekte na vaccinatie tegen gele koorts.

Millions of people are vaccinated each year to prevent morbidity and mortality by numerous bacterial and viral infections. Safety of vaccines is an important topic of discussion, especially because of the prophylactic nature of vaccination. Luckily, serious adverse events are rare. However, low incidence results in low awareness, and thus can make identification of these post-vaccination diseases difficult for healthcare workers. In the Netherlands, serious adverse events caused by travel vaccinations are especially rare, because of the low immunisation coverage compared to endemic countries. We present two Dutch cases that were diagnostically challenging. Both turned out to suffer from a serious adverse event of vaccination with live attenuated yellow fever virus, so-called yellow fever associated neurotropic disease (YEL-AND). With this article we hope to improve awareness of post-vaccination diseases, and YEL-AND in particular.

PReVENT--protective ventilation in patients without ARDS at start of ventilation: study protocol for a randomized controlled trial.

BACKGROUND: It is uncertain whether lung-protective mechanical ventilation using low tidal volumes should be used in all critically ill patients, irrespective of the presence of the acute respiratory distress syndrome (ARDS). A low tidal volume strategy includes use of higher respiratory rates, which could be associated with increased sedation needs, a higher incidence of delirium, and an increased risk of patient-ventilator asynchrony and ICU-acquired weakness. Another alleged side-effect of low tidal volume ventilation is the risk of atelectasis. All of these could offset the beneficial effects of low tidal volume ventilation as found in patients with ARDS. METHODS/DESIGN: PReVENT is a national multicenter randomized controlled trial in invasively ventilated ICU patients without ARDS with an anticipated duration of ventilation of longer than 24 hours in 5 ICUs in The Netherlands. Consecutive patients are randomly assigned to a low tidal volume strategy using tidal volumes from 4 to 6 ml/kg predicted body weight (PBW) or a high tidal volume ventilation strategy using tidal volumes from 8 to 10 ml/kg PBW. The primary endpoint is the number of ventilator-free days and alive at day 28. Secondary endpoints include ICU and hospital length of stay (LOS), ICU and hospital mortality, the incidence of pulmonary complications, including ARDS, pneumonia, atelectasis, and pneumothorax, the cumulative use and duration of sedatives and neuromuscular blocking agents, incidence of ICU delirium, and the need for decreasing of instrumental dead space. DISCUSSION: PReVENT is the first randomized controlled trial comparing a low tidal volume strategy with a high tidal volume strategy, in patients without ARDS at onset of ventilation, that recruits a sufficient number of patients to test the hypothesis that a low tidal volume strategy benefits patients without ARDS with regard to a clinically relevant endpoint. TRIAL REGISTRATION: The trial is registered at www.clinicaltrials.gov under reference number NCT02153294 on 23 May 2014.

[Tubulo-interstitial nephritis in inflammatory bowel disease: extra-intestinal manifestation or drug toxicity?]. / Tubulo-interstitiële nefritis bij inflammatoire darmziekte: extra-intestinale manifestatie of geneesmiddeltoxiciteit?

Chronic inflammatory bowel disease (IBD) is seldom complicated by renal function disorder, but when this occurs the consequences are serious. In addition to the known effects of 5-aminosalicylates, there is also evidence that tubulo-interstitial nephritis (TIN) occurs as an extra-intestinal manifestation of IBD. A 27-year-old woman with colitis ulcerosa, developed end-stage renal insufficiency due to a mesalazine-induced TIN. She was treated by haemodialysis for two years before she underwent renal transplantation. Another patient, a 36-year-old man with Crohn's disease, developed extensive granulomatous nephritis with stable moderate renal function. After excluding other possible causes, we diagnosed an extra-intestinal manifestation of his Crohn's disease. There are no official guidelines on renal function monitoring in IBD patients, nor is there consensus in literature. We advise renal monitoring after three months of treatment with 5-aminosalicylates, followed by monitoring every year. Patients not receiving treatment should be monitored every year.

Early determinants of long-term T-cell reconstitution after hematopoietic stem cell transplantation for severe combined immunodeficiency.

The immune system of patients with severe combined immunodeficiency (SCID) reconstitutes to a large extent during the first years after hematopoietic stem cell transplantation (HSCT). It was suggested, however, that accelerated loss of thymus output may cause impaired immune function at the long term. To address this issue, we studied patients with SCID who underwent allogeneic HSCT 5 to 32 years earlier and identified early determinants of long-term T-cell reconstitution. A variety of immune parameters were analyzed both early (1-4 years) and late (5-32 years) after HSCT. Late after HSCT, a clear distinction could be made between a group of 8 patients with impaired T-cell reconstitution and 11 patients with good immune reconstitution. Importantly, in patients with decreased long-term T-cell reconstitution, T-cell recovery was already poor early after HSCT, demonstrating that long-term immune failure was not caused by accelerated loss of thymus output or long-term graft failure, but resulted from poor early grafting. The number of T-cell receptor excision circles (TRECs) early after HSCT was most predictive for long-term T-cell reconstitution. Frequent monitoring of T-cell immunity and TREC numbers early after HSCT may thus serve to timely identify patients who will fail to reconstitute properly and who may need additional treatment.