COVID-19 in three waves in a tertiary referral hospital in Belgium: a comparison of patient characteristics, management, and outcome.

PURPOSE: Few studies have compared patient characteristics, clinical management, and outcome of patients with COVID-19 between the different epidemic waves. In this study, we describe patient characteristics, treatment, and outcome of patients admitted for COVID-19 in the Antwerp University Hospital over the first three epidemic waves of 2020-2021. METHODS: Retrospective observational study of COVID-19 patients in a Belgian tertiary referral hospital. All adult patients with COVID-19, hospitalized between February 29, 2020, and June 30, 2021, were included. Standardized routine medical data was collected from patient records. Risk factors were assessed with multivariable logistic regression. RESULTS: We included 722 patients, during the first (n = 179), second (n = 347) and third (n = 194) wave. We observed the lowest disease severity at admission during the first wave, and more elderly and comorbid patients during the second wave. Throughout the subsequent waves we observed an increasing use of corticosteroids and high-flow oxygen therapy. In spite of increasing number of complications throughout the subsequent waves, mortality decreased each wave (16.6%,15.6% 11.9% in 1st, 2nd and 3rd wave respectively). C-reactive protein above 150 mg/L was predictive for the need for intensive care unit admission (odds ratio (OR) 3.77, 95% confidence interval (CI) 2.32-6.15). A Charlson comorbidity index ≥ 5 (OR 5.68, 95% CI 2.54-12.70) and interhospital transfers (OR 3.78, 95% CI 2.05-6.98) were associated with a higher mortality. CONCLUSIONS: We observed a reduction in mortality each wave, despite increasing comorbidity. Evolutions in patient management such as high-flow oxygen therapy on regular wards and corticosteroid use may explain this favorable evolution.

Reoperation for bleeding after cardiac surgery.

BACKGROUND: Postoperative cardio-surgical haemostatic management is centre-specific and experience-based, which leads to a variability in patient care. This study aimed to identify which postoperative haemostatic interventions may reduce the need for reoperation after cardiac surgery in adults. METHODS: A retrospective case-control study in a tertiary centre. Adult, elective, primary cardiac surgical patients were selected (n = 2098); cases (n = 42) were patients who underwent reoperation within 72 h after the initial surgery. Interventions administered to control surgical bleeding were compared for the need to re-operate using multiple logistic regression. RESULTS: Rate of cardiac surgical reoperation was 2% in the study population. Three variables were found to be associated with cardiac reoperation: preoperative administration of fresh frozen plasma (OR 5.45, CI 2.34-12.35), cumulative volume of chest tube drainage and cumulative count of packed red blood cells transfusion on ICU (OR 1.98, CI 1.56-2.51). CONCLUSION: No significant difference among specific types of postoperative haemostatic interventions was found between patients who needed reoperation and those who did not. Perioperative transfusion of fresh frozen plasma, postoperative transfusion of packed cells and cumulative volume of chest tube drainage were associated with reoperation after cardiac surgery. These variables could help predict the need for reoperation.

Beta-Trace Protein as a Potential Marker of Acute Kidney Injury: A Pilot Study.

INTRODUCTION: Acute kidney injury (AKI) is a frequent complication among patients in the intensive care unit (ICU). The limitations of serum Cr (sCr) in timely detecting AKI are well known. Beta-trace protein (BTP) is emerging as a novel endogenous glomerular filtration rate marker. The aim of this study was to explore the role of BTP as a marker of AKI. METHODS: Patients admitted to the ICU undergoing surgery were included. BTP, sCr, Cystatin C (CysC), and neutrophil gelatinase-associated lipocalin (NGAL) were measured preoperatively, postoperatively (post-op), and at the first (D1) and second (D2) post-op day. AKI was defined as an increase of sCr to ≥1.5-fold from baseline within 2 days after surgery. RESULTS: Of the 52 patients studied, 10 patients (19%) developed AKI. Patients with AKI were older (69.6 ± 10.7 vs. 58.1 ± 16.7 years, p = 0.043) and had a longer length of ICU stay (13 [IQR 6-49] vs. 6 [IQR 5-8] days, p = 0.032). Between the 2 groups, the evolution of BTP, sCr, CysC, and NGAL over time differed significantly, with overall higher values in the AKI group. ROC analysis for the detection of AKI within 2 days after surgery showed a great accuracy for BTP. The area under the curve (AUC) for BTP post-op; D1; and D2 was, respectively, 0.869 ± 0.049; 0.938 ± 0.035; and 0.943 ± 0.032. The discriminative power of a BTP measurement on D1 was superior in detecting AKI compared to NGAL (adjusted p value = 0.027). We could not detect a significant difference between the AUCs of other biomarkers (NGAL, sCr, and CysC). CONCLUSION: Serum BTP is a promising marker for diagnosing AKI in ICU patients undergoing surgery.

Decontamination Strategies and Bloodstream Infections With Antibiotic-Resistant Microorganisms in Ventilated Patients: A Randomized Clinical Trial.

Importance: The effects of chlorhexidine (CHX) mouthwash, selective oropharyngeal decontamination (SOD), and selective digestive tract decontamination (SDD) on patient outcomes in ICUs with moderate to high levels of antibiotic resistance are unknown. Objective: To determine associations between CHX 2%, SOD, and SDD and the occurrence of ICU-acquired bloodstream infections with multidrug-resistant gram-negative bacteria (MDRGNB) and 28-day mortality in ICUs with moderate to high levels of antibiotic resistance. Design, Setting, and Participants: Randomized trial conducted from December 1, 2013, to May 31, 2017, in 13 European ICUs where at least 5% of bloodstream infections are caused by extended-spectrum ß-lactamase-producing Enterobacteriaceae. Patients with anticipated mechanical ventilation of more than 24 hours were eligible. The final date of follow-up was September 20, 2017. Interventions: Standard care was daily CHX 2% body washings and a hand hygiene improvement program. Following a baseline period from 6 to 14 months, each ICU was assigned in random order to 3 separate 6-month intervention periods with either CHX 2% mouthwash, SOD (mouthpaste with colistin, tobramycin, and nystatin), or SDD (the same mouthpaste and gastrointestinal suspension with the same antibiotics), all applied 4 times daily. Main Outcomes and Measures: The occurrence of ICU-acquired bloodstream infection with MDRGNB (primary outcome) and 28-day mortality (secondary outcome) during each intervention period compared with the baseline period. Results: A total of 8665 patients (median age, 64.1 years; 5561 men [64.2%]) were included in the study (2251, 2108, 2224, and 2082 in the baseline, CHX, SOD, and SDD periods, respectively). ICU-acquired bloodstream infection with MDRGNB occurred among 144 patients (154 episodes) in 2.1%, 1.8%, 1.5%, and 1.2% of included patients during the baseline, CHX, SOD, and SDD periods, respectively. Absolute risk reductions were 0.3% (95% CI, -0.6% to 1.1%), 0.6% (95% CI, -0.2% to 1.4%), and 0.8% (95% CI, 0.1% to 1.6%) for CHX, SOD, and SDD, respectively, compared with baseline. Adjusted hazard ratios were 1.13 (95% CI, 0.68-1.88), 0.89 (95% CI, 0.55-1.45), and 0.70 (95% CI, 0.43-1.14) during the CHX, SOD, and SDD periods, respectively, vs baseline. Crude mortality risks on day 28 were 31.9%, 32.9%, 32.4%, and 34.1% during the baseline, CHX, SOD, and SDD periods, respectively. Adjusted odds ratios for 28-day mortality were 1.07 (95% CI, 0.86-1.32), 1.05 (95% CI, 0.85-1.29), and 1.03 (95% CI, 0.80-1.32) for CHX, SOD, and SDD, respectively, vs baseline. Conclusions and Relevance: Among patients receiving mechanical ventilation in ICUs with moderate to high antibiotic resistance prevalence, use of CHX mouthwash, SOD, or SDD was not associated with reductions in ICU-acquired bloodstream infections caused by MDRGNB compared with standard care. Trial Registration: ClinicalTrials.gov Identifier: NCT02208154.

The course of diaphragm atrophy in ventilated patients assessed with ultrasound: a longitudinal cohort study.

INTRODUCTION: Mechanical ventilation and the effect of respiratory muscle unloading on the diaphragm cause ventilator-induced diaphragmatic dysfunction (VIDD). Atrophy of the diaphragmatic muscle is a major part of VIDD, and has a rapid onset in most animal models. We wanted to assess the clinical evolution and risk factors for VIDD in an adult intensive care unit (ICU) by measuring diaphragm thickness using ultrasound. METHOD: We performed a single-centre observational cohort study, including 54 mechanically ventilated patients. The right hemidiaphragm was measured daily at the zone of apposition on the midaxillary line. RESULTS: Mean baseline thickness was 1.9 mm (SD ± 0.4 mm), and mean nadir was 1.3 mm (SD ± 0.4 mm), corresponding with a mean change in thickness of 32 % (95 % CI 27-37 %). Length of mechanical ventilation (MV) was associated with the degree of atrophy, whereas other known risk factors for muscle atrophy in an ICU were not. The largest decrease in thickness occurred during the first 72 hours of MV. CONCLUSIONS: Diaphragm atrophy occurs quickly in mechanically ventilated patients and can accurately be monitored using ultrasound. Length of MV, as opposed to other variables, is associated with the degree of atrophy. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov NCT02299986 . Registered 10/11/2014.

Incidence and predisposing factors for the development of disturbed glucose metabolism and DIabetes mellitus AFter Intensive Care admission: the DIAFIC study.

INTRODUCTION: Elevated blood glucose levels during intensive care unit (ICU) stay, so-called stress hyperglycaemia (SH), is a common finding. Its relation with a future diabetes risk is unclear. Our objective was to determine the incidence of disturbed glucose metabolism (DGM) post ICU admission and to identify predictors for future diabetes risk with a focus on stress hyperglycaemia. METHODS: This single center prospective cohort trial (DIAFIC trial) had a study period between September 2011 and March 2013, with follow-up until December 2013. The setting was a mixed medical/surgical ICU in a tertiary teaching hospital in Belgium. 338 patients without known diabetes mellitus were included for analysis. We assessed the level of glucose metabolism disturbance (as diagnosed with a 75 g oral glucose tolerance test (OGTT) and/or HbA1c level) eight months after ICU admission, and investigated possible predictors including stress hyperglycaemia. RESULTS: In total 246 patients (73 %) experienced stress hyperglycaemia during the ICU stay. Eight months post-ICU admission, 119 (35 %) subjects had a disturbed glucose metabolism, including 24 (7 %) patients who were diagnosed with diabetes mellitus. A disturbed glucose metabolism tended to be more prevalent in subjects who experienced stress hyperglycaemia during ICU stay as compared to those without stress hyperglycaemia (38 % vs. 28 %, P = 0.065). HbA1c on admission correlated with the degree of stress hyperglycaemia. A diabetes risk score (FINDRISC) (11.0 versus 9.5, P = 0.001), the SAPS3 score (median of 42 in both groups, P = 0.003) and daily caloric intake during ICU stay (197 vs. 222, P = 0.011) were independently associated with a disturbed glucose metabolism. CONCLUSIONS: Stress hyperglycaemia is frequent in non-diabetic patients and predicts a tendency towards disturbances in glucose metabolism and diabetes mellitus. Clinically relevant predictors of elevated risk included a high FINDRISC score and a high SAPS3 score. These predictors can provide an efficient, quick and inexpensive way to identify patients at risk for a disturbed glucose metabolism or diabetes, and could facilitate prevention and early treatment. TRIAL REGISTRATION: At ClinicalTrials.gov NCT02180555 . Registered 1 July, 2014.

Falsely elevated sodium levels during thiopental treatment in the ICU: technical interference on a laboratory device with important clinical relevance.

INTRODUCTION: Thiopental is a cornerstone in the treatment of refractory status epilepticus and intractable intracranial hypertension. In our center we observed that thiopental might cause falsely elevated serum sodium levels. METHODS: Triggered by a recent case experience of extremely elevated serum sodium levels during thiopental treatment, we retrospectively identified 53 patients treated with thiopental in our intensive care unit between 2007 and 2011 and evaluated electrolyte changes. We differentiated the analysis before and after introduction of a new device for sodium assays (Dimension Vista, Siemens) in the central laboratory in April 2010. Standardized in vitro laboratory tests were performed to study the effect of thiopental on sodium analysis. RESULTS: Before April 2010, serum sodium levels determined in the central laboratory showed a good agreement with the bedside point-of-care (POC) device during thiopental therapy with [sodium](laboratory) - [sodium](POC) of only 1.08 mmol/L (P = .0517). After April 2010, a strong discrepancy between laboratory values and POC values was observed with [sodium](laboratory) - [sodium](POC) = 11.57 mmol/L (P < .0001). Standardized in vitro testing confirmed that thiopental induced a dose-dependent false hypernatremia (P = .002). CONCLUSIONS: Thiopental treatment can result in falsely elevated serum sodium. This is a critical finding since high sodium levels preclude administrating mannitol or hypertonic saline for the treatment of elevated intracranial pressure. Moreover, a false high sodium level might lead to the inappropriate administration of hypotonic fluids potentially resulting in increased brain edema and even higher intracranial pressure. To our knowledge, this is the first paper describing this clinically relevant phenomenon.

Unapparent systemic effects of regional anticoagulation with citrate in continuous renal replacement therapy: a narrative review.

The use of citrate, through reversible binding of calcium, has become the preferred choice for anticoagulation in continuous renal replacement therapy in the critically ill patient. Though generally considered as very efficacious in acute kidney injury, this type of anticoagulation can cause acid-base disorders as well as citrate accumulation and overload, phenomena which have been well described. The purpose of this narrative review is to provide an overview of some other, non-anticoagulation effects of citrate chelation during its use as anticoagulant. We highlight the effects seen on the calcium balance and hormonal status, phosphate and magnesium balance, as well as oxidative stress resulting from these unapparent effects. As most of these data on these non-anticoagulation effects have been obtained in small observational studies, new and larger studies documenting both short- and long-term effects should be undertaken. Subsequent future guidelines for citrate-based continuous renal replacement therapy should take not only the metabolic but also these unapparent effects into account.

Regional Citrate Anticoagulation in Continuous Renal Replacement Therapy: Is Metabolic Fear the Enemy of Logic? A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

BACKGROUND: Anticoagulation is recommended to maintain the patency of the circuit in continuous renal replacement therapy (CRRT). However, anticoagulation-associated complications can occur. We performed a systematic review and meta-analysis to compare the efficacy and safety of citrate anticoagulation to heparin anticoagulation in critically ill patients treated with CRRT. METHODS: Randomised controlled trials (RCTs) evaluating the safety and efficacy of citrate anticoagulation and heparin in CRRT were included. Articles not describing the incidence of metabolic and/or electrolyte disturbances induced by the anticoagulation strategy were excluded. The PubMed, Embase, and MEDLINE electronic databases were searched. The last search was performed on 18 February 2022. RESULTS: Twelve articles comprising 1592 patients met the inclusion criteria. There was no significant difference between the groups in the development of metabolic alkalosis (RR = 1.46; (95% CI (0.52-4.11); p = 0.470)) or metabolic acidosis (RR = 1.71, (95% CI (0.99-2.93); p = 0.054)). Patients in the citrate group developed hypocalcaemia more frequently (RR = 3.81; 95% CI (1.67-8.66); p = 0.001). Bleeding complications in patients randomised to the citrate group were significantly lower than those in the heparin group (RR 0.32 (95% CI (0.22-0.47); p < 0.0001)). Citrate showed a significantly longer filter lifespan of 14.52 h (95% CI (7.22-21.83); p < 0.0001), compared to heparin. There was no significant difference between the groups for 28-day mortality (RR = 1.08 (95% CI (0.89-1.31); p = 0.424) or 90-day mortality (RR 0.9 (95% CI (0.8-1.02); p = 0.110). CONCLUSION: regional citrate anticoagulation is a safe anticoagulant for critically ill patients who require CRRT, as no significant differences were found in metabolic complications between the groups. Additionally, citrate has a lower risk of bleeding and circuit loss than heparin.

Do-Not-ResuscitateDecision-Making during the COVID-19 Pandemic in a Teaching Hospital: Lessons Learned for the Future.

Method: A cross-sectional survey study was conducted between February 2021 and April 2021 for all doctors and doctors in training, working in the Antwerp University Hospital during the COVID-19 pandemic. Results: 127 doctors participated in this study. The familiarity with the different scores used in the triage during the COVID-10 pandemic was 51% for the Clinical Frailty Scale (CFS) and 20% for the Charlson Comorbidity Index (CCI). Participants indicated that their DNR decision is based on various aspects such as clinical assessment, comorbidities, patient's wishes, age, prognosis, and functional state. Conclusion: The familiarity with the different scores used during triage assessments is low. The total clinical picture of the patient is needed to make a considered decision, and this total picture of the patient seems to be well encompassed by frailty measurement (CFS). Although many participants indicated that the different scores do not offer much added value compared to their clinical assessment, it can help guide DNR decisions, especially for doctors in training.

Thrombotic microangiopathy after traumatic brain injury: A case report and review of the literature.

Key Clinical Message: This case report supports that trauma can rarely cause thrombotic microangiopathy (TMA). Early recognition is important due to a high mortality of untreated TMA, but diagnosis can be delayed by attributing lab abnormalities as due to blood loss. Abstract: Major trauma can provoke coagulopathy, ranging from hypo- to hypercoagulation. Thrombotic microangiopathy (TMA), characterized by hemolytic anemia, renal failure, thrombocytopenia, and intravascular hemolysis, results in bleeding tendency but also microvascular thrombosis. We report a rare case of isolated traumatic brain injury leading to TMA treated with plasmapheresis.

The effects of antibiotic cycling and mixing on acquisition of antibiotic resistant bacteria in the ICU: A post-hoc individual patient analysis of a prospective cluster-randomized crossover study.

BACKGROUND: Repeated rotation of empiric antibiotic treatment strategies is hypothesized to reduce antibiotic resistance. Clinical rotation studies failed to change unit-wide prevalence of antibiotic resistant bacteria (ARB) carriage, including an international cluster-randomized crossover study. Unit-wide effects may differ from individual effects due to "ecological fallacy". This post-hoc analysis of a cluster-randomized crossover study assesses differences between cycling and mixing rotation strategies in acquisition of carriage with Gram-negative ARB in individual patients. METHODS: This was a controlled cluster-randomized crossover study in 7 ICUs in 5 European countries. Clinical cultures taken as routine care were used for endpoint assessment. Patients with a first negative culture and at least one culture collected in total were included. Community acquisitions (2 days of admission or less) were excluded. Primary outcome was ICU-acquisition of Enterobacterales species with reduced susceptibility to: third- or fourth generation cephalosporins or piperacillin-tazobactam, and Acinetobacter species and Pseudomonas aeruginosa with reduced susceptibility for piperacillin-tazobactam or carbapenems. Cycling (altering first-line empiric therapy for Gram-negative bacteria, every other 6-weeks), to mixing (changing antibiotic type every empiric antibiotic course). Rotated antibiotics were third- or fourth generation cephalosporins, piperacillin-tazobactam and carbapenems. RESULTS: For this analysis 1,613 admissions were eligible (855 and 758 during cycling and mixing, respectively), with 16,437 microbiological cultures obtained. Incidences of acquisition with ARB during ICU-stay were 7.3% (n = 62) and 5.1% (n = 39) during cycling and mixing, respectively (p-value 0.13), after a mean of 17.7 (median 15) and 20.8 (median 13) days. Adjusted odds ratio for acquisition of ARB carriage during mixing was 0.62 (95% CI 0.38 to 1.00). Acquired carriage with ARB were Enterobacterales species (n = 61), Pseudomonas aeruginosa (n = 38) and Acinetobacter species (n = 20), with no statistically significant differences between interventions. CONCLUSIONS: There was no statistically significant difference in individual patients' risk of acquiring carriage with Gram-negative ARB during cycling and mixing. These findings substantiate the absence of difference between cycling and mixing on the epidemiology of Gram-negative ARB in ICU. TRIAL REGISTRATION: This trial is registered with ClinicalTrials.gov, registered 10 January 2011, NCT01293071.

A retrospective observational study on the efficacy of colistin by inhalation as compared to parenteral administration for the treatment of nosocomial pneumonia associated with multidrug-resistant Pseudomonas aeruginosa.

BACKGROUND: Colistin is used as last treatment option for pneumonia associated with multidrug-resistant (MDR) Pseudomonas spp.. Literature about the best administration mode (inhalation versus parenteral treatment) is lacking. METHODS: A retrospective study of 20 intensive care patients with a pneumonia associated with MDR P. aeruginosa receiving colistin sulphomethate sodium (Colistineb®) between 2007 and 2009 was performed. A strain was considered multidrug-resistant if it was resistant to at least 6 of the following antibiotics: piperacillin-tazobactam, ceftazidime, cefepime, meropenem, aztreonam, ciprofloxacin, and amikacin. The administration mode, predicted mortality based on the SAPS3 score, SOFA score at onset of the colistin treatment, clinical and microbiological response, and mortality during the episode of the infection were analysed. The non parametric Kruskal-Wallis and Fisher's Exact test were used for statistical analysis of respectively the predicted mortality/SOFA score and mortality rate. RESULTS: Six patients received colistin by inhalation only, 5 were treated only parenterally, and 9 by a combination of both administration modes. All patients received concomitant beta-lactam therapy. The mean predicted mortalities were respectively 72%, 68%, and 69% (p = 0.91). SOFA scores at the onset of the treatment were also comparable (p = 0.87). Clinical response was favorable in all patients receiving colistin by inhalation (6/6) and in 40% (2/5) of the patients receiving colistin parenterally (p = 0.06). In the patients with colistin administered both via inhalation and parenterally, clinical response was favorable in 78% of the patients (7/9) (p = 0.27 as compared to the treatment group receiving colistin only parenterally). When all patients with inhalation therapy were compared to the group without inhalation therapy, a favorable clinical response was present in respectively 87% and 40% (p = 0.06). In none of the patients, the Pseudomonas spp. was eradicated from the follow-up cultures.All patients in the parenterally treated group died. None of the patients receiving colistin by inhalation, and 3 of 9 patients of the combination group eventually died (p = 0.002 and p = 0.03 respectively as compared to the group receiving colistin only parenterally). CONCLUSIONS: Aerosolized colistin could be beneficial as adjunctive treatment for the management of pneumonia due to MDR P. aeruginosa.

Neurally adjusted ventilatory assist: a ventilation tool or a ventilation toy?

Mechanical ventilation has, since its introduction into clinical practice, undergone a major evolution from controlled ventilation to various modes of assisted ventilation. Neurally adjusted ventilatory assist (NAVA) is the newest development. The implementation of NAVA requires the introduction of a catheter to measure the electrical activity of the diaphragm (EA(di)). NAVA relies, opposite to conventional assisted ventilation modes, on the EA(di) to trigger the ventilator breath and to adjust the ventilatory assist to the neural drive. The amplitude of the ventilator assist is determined by the instantaneous EA(di) and the NAVA level set by the clinician. The NAVA level amplifies the EA(di) signal and determines instantaneous ventilator assist on a breath-to-breath basis. Experimental and clinical data suggest superior patient-ventilator synchrony with NAVA. Patient-ventilator asynchrony is present in 25% of mechanically ventilated patients in the intensive care unit and may contribute to patient discomfort, sleep fragmentation, higher use of sedation, development of delirium, ventilator-induced lung injury, prolonged mechanical ventilation, and ultimately mortality. With NAVA, the reliance on the EA(di) signal, together with an intact ventilatory drive and intact breathing reflexes, allows integration of the ventilator in the neuro-ventilatory coupling on a higher level than conventional ventilation modes. The simple monitoring of the EA(di) signal alone may provide the clinician with important information to guide ventilator management, especially during the weaning process. Although, until now, little evidence proves the superiority of NAVA on clinically relevant end points, it seems evident that patient populations (eg, COPD and small children) with major patient-ventilator asynchrony may benefit from this new ventilatory tool.

Two unusual pediatric cases of dilutional hyponatremia.

Dilutional hyponatremia, although not uncommon, is an underestimated problem in the pediatric population. In most cases, it results from excessive hydration or water retention, also described as the so-called water intoxication. One of the most known causes is the use of desmopressin in enuretic children. This drug enhances the free water reabsorption in the renal collecting ducts. The addition of the anticholinergic agent oxybutynin aggravated the condition by causing a dry mouth with excessive thirst and water intake in our first case. Dietary water overconsumption, either voluntary or involuntary, is a phenomenon seen in formula-fed babies. But in our second case, a game involving forced ingestion of large amounts of water had serious consequences including hyponatremia-related coma. An effort should therefore be made to inform caretakers about the risks of these games. These cases, provoked by rather unusual and peculiar causes, illustrate again that electrolytes and especially serum [Na(+)] are key points to be determined in a child with diminished consciousness. Moreover, an accurate history including the intake of medication and dietary information should be made.

Pre-admission air pollution exposure prolongs the duration of ventilation in intensive care patients.

PURPOSE: Air pollutant exposure constitutes a serious risk factor for the emergence or aggravation of (existing) pulmonary disease. The impact of pre-intensive care ambient air pollutant exposure on the duration of artificial ventilation was, however, not yet established. METHODS: The medical records of 2003 patients, admitted to the intensive care unit (ICU) of the Antwerp University Hospital (Flanders, Belgium), who were artificially ventilated on ICU admission or within 48 h after admission, for the duration of at least 48 h, were analyzed. For each patient's home address, daily air pollutant exposure [particulate matter with an aerodynamic diameter ≤ 2.5 µm (PM2.5) and ≤ 10 µm (PM10), nitrogen dioxide (NO2) and black carbon (BC)] up to 10 days prior to hospital admission was modeled using a high-resolution spatial-temporal model. The association between duration of artificial ventilation and air pollution exposure during the last 10 days before ICU admission was assessed using distributed lag models with a negative binomial regression fit. RESULTS: Controlling for pre-specified confounders, an IQR increment in BC (1.2 µg/m3) up to 10 days before admission was associated with an estimated cumulative increase of 12.4% in ventilation duration (95% CI 4.7-20.7). Significant associations were also observed for PM2.5, PM10 and NO2, with cumulative estimates ranging from 7.8 to 8.0%. CONCLUSION: Short-term ambient air pollution exposure prior to ICU admission represents an unrecognized environmental risk factor for the duration of artificial ventilation in the ICU.

154 compared to 54 mmol per liter of sodium in intravenous maintenance fluid therapy for adult patients undergoing major thoracic surgery (TOPMAST): a single-center randomized controlled double-blind trial.

PURPOSE: To determine the effects of the sodium content of maintenance fluid therapy on cumulative fluid balance and electrolyte disorders. METHODS: We performed a randomized controlled trial of adults undergoing major thoracic surgery, randomly assigned (1:1) to receive maintenance fluids containing 154 mmol/L (Na154) or 54 mmol/L (Na54) of sodium from the start of surgery until their discharge from the ICU, the occurrence of a serious adverse event or the third postoperative day at the latest. Investigators, caregivers and patients were blinded to the treatment. Primary outcome was cumulative fluid balance. Electrolyte disturbances were assessed as secondary endpoints, different adverse events and physiological markers as safety and exploratory endpoints. FINDINGS: We randomly assigned 70 patients; primary outcome data were available for 33 and 34 patients in the Na54 and Na154 treatment arms, respectively. Estimated cumulative fluid balance at 72 h was 1369 mL (95% CI 601-2137) more positive in the Na154 arm (p < 0.001), despite comparable non-study fluid sources. Hyponatremia < 135 mmol/L was encountered in four patients (11.8%) under Na54 compared to none under Na154 (p = 0.04), but there was no significantly more hyponatremia < 130 mmol/L (1 versus 0; p = 0.31). There was more hyperchloremia > 109 mmol/L under Na154 (24/35 patients, 68.6%) than under Na54 (4/34 patients, 11.8%) (p < 0.001). The treating clinicians discontinued the study due to clinical or radiographic fluid overload in six patients receiving Na154 compared to one patient under Na54 (excess risk 14.2%; 95% CI - 0.2-30.4%, p = 0.05). CONCLUSIONS: In adult surgical patients, sodium-rich maintenance solutions were associated with a more positive cumulative fluid balance and hyperchloremia; hypotonic fluids were associated with mild and asymptomatic hyponatremia.

Maintenance fluid therapy and fluid creep impose more significant fluid, sodium, and chloride burdens than resuscitation fluids in critically ill patients: a retrospective study in a tertiary mixed ICU population.

PURPOSE: Research on intravenous fluid therapy and its side effects, volume, sodium, and chloride overload, has focused almost exclusively on the resuscitation setting. We aimed to quantify all fluid sources in the ICU and assess fluid creep, the hidden and unintentional volume administered as a vehicle for medication or electrolytes. METHODS: We precisely recorded the volume, sodium, and chloride burdens imposed by every fluid source administered to 14,654 patients during the cumulative 103,098 days they resided in our 45-bed tertiary ICU and simulated the impact of important strategic fluid choices on patients' chloride burdens. In septic patients, we assessed the impact of the different fluid sources on cumulative fluid balance, an established marker of morbidity. RESULTS: Maintenance and replacement fluids accounted for 24.7% of the mean daily total fluid volume, thereby far exceeding resuscitation fluids (6.5%) and were the most important sources of sodium and chloride. Fluid creep represented a striking 32.6% of the mean daily total fluid volume [median 645 mL (IQR 308-1039 mL)]. Chloride levels can be more effectively reduced by adopting a hypotonic maintenance strategy [a daily difference in chloride burden of 30.8 mmol (95% CI 30.5-31.1)] than a balanced resuscitation strategy [daily difference 3.0 mmol (95% CI 2.9-3.1)]. In septic patients, non-resuscitation fluids had a larger absolute impact on cumulative fluid balance than did resuscitation fluids. CONCLUSIONS: Inadvertent daily volume, sodium, and chloride loading should be avoided when prescribing maintenance fluids in view of the vast amounts of fluid creep. This is especially important when adopting an isotonic maintenance strategy.

The effects of antibiotic cycling and mixing on antibiotic resistance in intensive care units: a cluster-randomised crossover trial.

BACKGROUND: Whether antibiotic rotation strategies reduce prevalence of antibiotic-resistant, Gram-negative bacteria in intensive care units (ICUs) has not been accurately established. We aimed to assess whether cycling of antibiotics compared with a mixing strategy (changing antibiotic to an alternative class for each consecutive patient) would reduce the prevalence of antibiotic-resistant, Gram-negative bacteria in European intensive care units (ICUs). METHODS: In a cluster-randomised crossover study, we randomly assigned ICUs to use one of three antibiotic groups (third-generation or fourth-generation cephalosporins, piperacillin-tazobactam, and carbapenems) as preferred empirical treatment during 6-week periods (cycling) or to change preference after every consecutively treated patient (mixing). Computer-based randomisation of intervention and rotated antibiotic sequence was done centrally. Cycling or mixing was applied for 9 months; then, following a washout period, the alternative strategy was implemented. We defined antibiotic-resistant, Gram-negative bacteria as Enterobacteriaceae with extended-spectrum ß-lactamase production or piperacillin-tazobactam resistance, and Acinetobacter spp and Pseudomonas aeruginosa with piperacillin-tazobactam or carbapenem resistance. Data were collected for all admissions during the study. The primary endpoint was average, unit-wide, monthly point prevalence of antibiotic-resistant, Gram-negative bacteria in respiratory and perineal swabs with adjustment for potential confounders. This trial is registered with ClinicalTrials.gov, number NCT01293071. FINDINGS: Eight ICUs (from Belgium, France, Germany, Portugal, and Slovenia) were randomly assigned and patients enrolled from June 27, 2011, to Feb 16, 2014. 4069 patients were admitted during the cycling periods in total and 4707 were admitted during the mixing periods. Of these, 745 patients during cycling and 853 patients during mixing were present during the monthly point-prevalence surveys, and were included in the main analysis. Mean prevalence of the composite primary endpoint was 23% (168/745) during cycling and 22% (184/853) during mixing (p=0·64), yielding an adjusted incidence rate ratio during mixing of 1·039 (95% CI 0·837-1·291; p=0·73). There was no difference in all-cause in-ICU mortality between intervention periods. INTERPRETATION: Antibiotic cycling does not reduce the prevalence of carriage of antibiotic-resistant, Gram-negative bacteria in patients admitted to the ICU. FUNDING: European Union Seventh Framework Programme.