Electrolyte monitoring during regional citrate anticoagulation in continuous renal replacement therapy.

Patients with acute kidney injury who need continuous renal replacement therapy with locoregional citrate anticoagulation are at risk of citrate accumulation with disruption of the calcium balance. We aimed to evaluate the safety of detecting citrate accumulation and adjusting electrolyte disbalances during continuous venovenous hemodialysis (CVVHD) in critically ill patients with acute kidney injury using a blood sample frequency every 6 h. A prospective single center study in critically ill intensive care unit patients who suffered from acute kidney injury with the need of renal replacement therapy. We evaluated the deviations in pH, bicarbonate and calcium during CVVHD treatment with local regional citrate anticoagulation. Values indicate median and interquartile range. Severe hypocalcemia (below 1.04 mmol/L) or hypercalcemia (above 1.31 mmol/L) occurred in 10.5% and 4.8% respectively. During treatment changes of systemic ionized calcium, post-filter ionized calcium, pH and bicarbonate were corrected with protocolized adjustments. No arrhythmias or citrate accumulation were seen. The values stabilized after 42 h and after that no statistically significant changes were observed. After 42 h of citrate CVVHD, systemic ionized calcium, pH and bicarbonate levels stabilized. A blood sample frequency every 6 h is probably safe to detect citrate accumulation and to adjust the settings of electrolytes to avoid serious electrolyte disturbances in ICU patients without severe metabolic acidosis or severe liver failure.

Nephrotoxicity of continuous amphotericin B in critically ill patients with abdominal sepsis: a retrospective analysis with propensity score matching.

BACKGROUND: Continuous infusion of conventional amphotericin B (CCAB) is used in ICUs for pre-emptive treatment of invasive fungal infections. Amphotericin B has previously been associated with nephrotoxicity. OBJECTIVES: To investigate if CCAB with therapeutic drug monitoring (TDM) results in renal impairment over time in critically ill patients with abdominal sepsis. PATIENTS AND METHODS: The study was conducted at mixed medical-surgical ICUs of two large teaching hospitals in the Netherlands. Consecutive patients who were treated on the ICUs between 2006 and 2019 for abdominal sepsis, with or without CCAB, were included. CCAB dosing was guided by TDM. Serum creatinine concentrations and renal failure scores of patients with CCAB treatment were compared with those without CCAB treatment. Excluded were: (i) patients treated with CCAB for less than 72 h; and (ii) patients with renal replacement therapy. RESULTS: A total of 319 patients were included (185 treated with CCAB and 134 controls). A multiple linear regression model showed that the serum creatinine concentration was independent of CCAB treatment (ß = -0.023; 95% CI = -12.2 to 7.2; P = 0.615). Propensity score matching resulted in 134 pairs of CCAB-treated and non-treated patients. Again, the analysis of these pairs showed that the cumulative CCAB dose was not associated with serum creatinine concentration during intensive care treatment (ß = 0.299; 95% CI = -0.38 to 0.98; P = 0.388). CONCLUSIONS: CCAB with TDM did not result in renal impairment over time in critically ill patients with abdominal sepsis.

Clinically relevant potential drug-drug interactions in intensive care patients: A large retrospective observational multicenter study.

PURPOSE: Potential drug-drug interactions (pDDIs) may harm patients admitted to the Intensive Care Unit (ICU). Due to the patient's critical condition and continuous monitoring on the ICU, not all pDDIs are clinically relevant. Clinical decision support systems (CDSSs) warning for irrelevant pDDIs could result in alert fatigue and overlooking important signals. Therefore, our aim was to describe the frequency of clinically relevant pDDIs (crpDDIs) to enable tailoring of CDSSs to the ICU setting. MATERIALS & METHODS: In this multicenter retrospective observational study, we used medication administration data to identify pDDIs in ICU admissions from 13 ICUs. Clinical relevance was based on a Delphi study in which intensivists and hospital pharmacists assessed the clinical relevance of pDDIs for the ICU setting. RESULTS: The mean number of pDDIs per 1000 medication administrations was 70.1, dropping to 31.0 when considering only crpDDIs. Of 103,871 ICU patients, 38% was exposed to a crpDDI. The most frequently occurring crpDDIs involve QT-prolonging agents, digoxin, or NSAIDs. CONCLUSIONS: Considering clinical relevance of pDDIs in the ICU setting is important, as only half of the detected pDDIs were crpDDIs. Therefore, tailoring CDSSs to the ICU may reduce alert fatigue and improve medication safety in ICU patients.

How to improve patient safety and quality of care in breast implant surgery? First outcomes from the Dutch Breast Implant Registry (2015-2017).

BACKGROUND: Although the use of breast implants is generally considered to be safe, breast implants are associated with short- and long-term complications. To evaluate and improve the quality of breast implant surgery, and increase our knowledge of implant performance, the national Dutch Breast Implant Registry (DBIR) was established in 2015. DBIR is one of the first up-and-running breast implant registries worldwide and follows an opt-out structure. OBJECTIVE: This article provides an overview of the first outcomes and experiences of the DBIR. METHODS: The national coverage of DBIR was studied using data from the Dutch Health and Youth Care Inspectorate. The incidence rate of breast implants was calculated for 2016 and 2017, and patient, device, and surgery characteristics were compared between cosmetic breast augmentations or reconstructive indications. Four infection control, measures were selected to demonstrate the variation in the Dutch clinical practice. RESULTS: In 2016, 95% of the hospitals and 78% of the private clinics participated in DBIR. Between 2015 and 2017, a total of 15,049 patients and 30,541 breast implants were included. A minimum breast implant incidence rate of 1 per 1,691 women could be determined for 2017. The majority of devices were inserted for a cosmetic indication (85.2%). In general, patient, device, and surgery characteristics differed per indication group. Substantial variation was seen in the use of infection control measures (range 0-100%). CONCLUSION: Preliminary results obtained from DBIR show high national participation rates and support further developments toward the improvement of breast implant surgery and patient safety.

Hospital transfer after a breast cancer diagnosis: A population-based study in the Netherlands of the extent, predictive characteristics and its impact on time to treatment.

PURPOSE: Patients may transfer of hospital for clinical reasons but this may delay time to treatment. The purpose of this study is to provide insight in the extent of hospital transfer in breast cancer care; which type of patients transfer and what is the impact on time to treatment. METHODS: We included 41,413 breast cancer patients registered in the Netherlands Cancer Registry between 2014 and 2016. We investigated transfer of hospital between diagnosis and first treatment being surgery or neoadjuvant chemotherapy (NAC). Co-variate adjusted characteristics predictive for hospital transfer were determined. To adjust for possible treatment by indication bias we used propensity score matching (PSM). Time to treatment in patients with and without hospital transfer was compared. RESULTS: Among 41,413 patients, 8.5% of all patients transferred to another hospital between diagnosis and first treatment; 4.9% before primary surgery and 24.8% before NAC. Especially young (aged <40 years) patients and those who underwent a mastectomy with immediate breast reconstruction (IBR) were more likely to transfer. The association of mastectomy with IBR with hospital transfer remained when using PSM. Hospital transfer after diagnosis significantly prolonged time to treatment; breast-conserving surgery by 5 days, mastectomy by 7 days, mastectomy with IBR by 9 days and NAC by 1 day. CONCLUSIONS: While almost 5% of Dutch patients treated with primary surgery transfer hospital after diagnosis and up to 25% for patients treated with NAC, our findings suggest that especially those treated with primary surgery are at risk for additional treatment delay by hospital transfer.

Variation in the Use of Boost Irradiation in Breast-Conserving Therapy in the Netherlands: The Effect of a National Guideline and Cofounding Factors.

AIMS: To determine the variation in radiation therapy boost use in a nationwide study following adjustment of a national guideline in 2011, as well as to address the relationship to patient, tumour and radiation therapy institutional factors. MATERIALS AND METHODS: All invasive breast cancers and non-invasive breast cancers (ductal carcinoma in situ; DCIS) that received external whole-breast radiation between 2011 and 2016 were selected from the Netherlands Cancer Registry. Box plots were used to evaluate variation over time and logistic regression was carried out to address other factors influencing the variation. Funnel plots were constructed, with unadjusted and adjusted data for patient and tumour factors significantly affecting the use of a boost. RESULTS: For breast cancer patients (n = 45,207), the proportion receiving a boost and its range decreased over the years from 37.3-92.7% in 2011 to 28.3-65.4% in 2016. This trend was not observed in DCIS patients (n = 6,844). Young age, large tumours, high grade and the absence of tumour-free resection margins were associated with boost use for both breast cancer and DCIS. For breast cancer, triple-negative tumour subtype and metastatic lymph node involvement were also associated with boost use. Institutional factors did not influence the use of a boost and institutional variation remained substantial after case-mix adjustments. CONCLUSION: Following adjustment of a nationwide implemented guideline, variation in radiation therapy boost use decreased in patients with breast cancer but not in patients with DCIS. Several tumour and patient characteristics were associated with boost use. Substantial institutional variation could not be explained by differences in patient, tumour or predefined institutional characteristics.

Current decisions on neoadjuvant chemotherapy for early breast cancer: Experts' experiences in the Netherlands.

PURPOSE: To evaluate the opinion of surgical and medical oncologists on neoadjuvant chemotherapy (NAC) for early breast cancer. METHODS: Surgical and medical oncologists (N = 292) participating in breast cancer care in the Netherlands were invited for a 20-question survey on the influence of patient, disease, and management related factors on their decisions towards NAC. RESULTS: A total of 138 surgical and medical oncologists from 64 out of 89 different Dutch hospitals completed the survey. NAC was recommended for locally advanced breast cancer (94%) and for downstaging to enable breast conserving surgery (BCS) (75%). Despite willingness to downstage, 64% of clinicians routinely recommended NAC when systemic therapy was indicated preoperatively. Reported reasons to refrain from NAC are comorbidities (68%), age >70 years (52%), and WHO-performance status ≥2 (93%). Opinions on NAC and surgical management were inconclusive; while 75% recommends NAC to enable BCS, some stated that BCS after NAC increases the risk of a non-radical resection (21%), surgical complications (9%) and recurrence of disease (5%). CONCLUSION: This article emphasizes the need for more consensus among specialists on the indications for NAC in early BC patients. Unambiguous and evidence-based treatment information could improve doctor-patient communication, supporting the patient in chemotherapy timing decision-making.

Patients' experiences with decisions on timing of chemotherapy for breast cancer.

INTRODUCTION: Despite potential advantages, application of chemotherapy in the neo-adjuvant (NAC) instead of adjuvant (AC) setting for breast cancer (BC) patients varies among hospitals. The aim of this study was to gain insight in patients' experiences with decisions on the timing of chemotherapy for stage II and III BC. MATERIALS AND METHODS: A 35-item online questionnaire was distributed among female patients (age>18) treated with either NAC or AC for clinical stage II/III invasive BC in 2013-2014 in the Netherlands. Outcome measures were the experienced exchange of information on the possible choice between both options and patients' involvement in the final decision on chemotherapy timing. Chemotherapy treatment experience was measured with the Cancer Therapy Satisfaction Questionnaire (CTSQ). RESULTS: Of 805 invited patients, 49% responded (179 NAC, 215 AC). NAC-treated patients were younger and more often treated in teaching/academic hospitals and high-volume hospitals. Information on the possibility of NAC was given to a minority of AC-treated patients (AC, stage II:14%, stage III: 31%). Information on pros and cons of both NAC and AC was rated sufficient in about three fourth of respondents. Respondents not always felt having a choice in the timing of chemotherapy (stage II: 54% NAC vs 36% AC; stage III: 26% NAC, 54% AC). CONCLUSION: The need to make a treatment decision on NAC was found to be made explicit in only a small number of adjuvant treated patients, in particular in BC stage II. Less than half of the respondents felt they had a real choice.

Systematic review of the safety and efficacy of contrast injection via venous catheters for contrast-enhanced computed tomography.

OBJECTIVE: To examine the safety and efficacy of contrast injection through a central venous catheter (CVC) for contrast-enhanced computed tomography (CECT). METHODS: A systematic literature search was performed using PubMed. Studies were deemed eligible if they reported on the use of CVCs for contrast administration. Selected articles were assessed for their relevance and risk of bias. Articles with low relevance and high risk of bias or both were excluded. Data from included articles was extracted. RESULTS: Seven studies reported on the use of CVCs for contrast administration. Catheter rupture did not occur in any study. The incidence of dislocation ranged from 2.2-15.4%. Quality of scans was described in three studies, with less contrast enhancement of pulmonary arteries and the thoracic aorta in two studies, and average or above average quality in one study. Four other studies used higher flowrates, but did not report quality of scans. CONCLUSION: Contrast injection via CVCs can be performed safely for CECT when using a strict protocol. Quality of scans depended on multiple factors like flow rate, indication of the scan, and cardiac output of the patient. In each patient, an individual evaluation whether to use the CVC as access for contrast media should be made, while bolus tracking may be mandatory in most cases.

Variation in use of neoadjuvant chemotherapy in patients with stage III breast cancer: Results of the Dutch national breast cancer audit.

OBJECTIVES: Neoadjuvant chemotherapy (NAC) is important in the optimal treatment of patients with locally advanced (stage III) breast cancer (BC). The objective of this study was to examine the clinical practice of NAC for stage III BC patients in all Dutch hospitals participating in BC care. MATERIALS AND METHODS: All patients aged 18-70 years who received surgery for stage III BC from January 2011 to September 2015 were selected from the national multidisciplinary NABON Breast Cancer Audit. Multivariable logistic regression was used to assess independent predictors of NAC use, focussing on hospital factors. RESULTS: A total of 1230 out of 1556 patients with stage III BC (79%) received NAC prior to surgery. The use of NAC did not change over time. We observed a large variation of NAC use between hospitals (0-100%). Age <50 years, breast MRI, large tumour size, advanced nodal disease, negative hormone receptor status and hospital participation in neoadjuvant clinical studies were significant independent predictors of NAC use (all P < 0.001). NAC use in stage III BC was not influenced by hospital type and hospital surgical volume. After adjustment for all independent predictors, variation in NAC use between hospitals remained (0% to 97%). CONCLUSION: NAC was used in 79% of patients with stage III BC, which represent a high quality of care in the NL. Patient, tumour, clinical management and hospital factors could not explain considerable variation in its use between hospitals. Hospital participation in neoadjuvant studies did show to improve the use of NAC in daily practice.

Transient versus persistent acute kidney injury and the diagnostic performance of fractional excretion of urea in critically ill patients.

AIMS: To evaluate the performance of fractional excretion of urea (FeU) for differentiating transient (T) from persistent (P) acute kidney injury (AKI) and to assess performance of FeU in predicting AKI in patients admitted to the ICU. METHODS: We performed secondary analysis of a multicenter prospective observational cohort study on the predictive performance of biological markers for AKI in critically ill patients. AKI was diagnosed according to RIFLE staging. RESULTS: Of 150 patients, 51 and 41 patients were classified as having T-AKI and P-AKI, respectively. The diagnostic performance for FeU to discriminate T-AKI from P-AKI on the day of AKI was poor (AUC-ROC = 0.61; 95% CI: 0.49-0.73). The diagnostic performance of FeU to predict AKI 1 and 2 days prior to AKI was poor as well (AUC-ROC = 0.61; 95% CI: 0.47-0.74, and 0.58; 95% CI: 0.43-0.73, respectively). CONCLUSIONS: FeU does not seem to be helpful in differentiating T- from P-AKI in critically ill patients and it is a poor predictor of AKI.

Approach to hypophosphataemia in intensive care units - a nationwide survey.

BACKGROUND: Evidence-based guidelines for monitoring of serum phosphate levels and for the treatment of hypophosphataemia in critically ill patients are lacking. The aim of this survey was to evaluate current practice with respect to diagnosis and treatment of hypophosphataemia in critically ill patients among intensive care unit (ICU) physicians in the Netherlands. METHODS: A survey was conducted among all hospitals with an ICU in the Netherlands. Paediatric ICUs were excluded from participation. A questionnaire was sent, with questions on practice regarding serum phosphate monitoring and treatment of hypophosphataemia. Respondents returned the questionnaire either by mail or through a web-based survey. RESULTS: A response was received from 67÷89 ICUs (75%). Respondents mentioned renal replacement therapy, sepsis and malnutrition, as well as surgery involving cardiopulmonary bypass as the most important causes of hypophosphataemia in intensive care unit patients. Of all respondents, 46% reported to measure serum phosphate levels on a daily basis, whereas in 12% serum phosphate levels were measured only on clinical indication. Less than half of the respondents had some sort of guideline for correction of hypophosphataemia. In a vast majority (79%), correction of hypophosphataemia was reported to start with serum phosphate levels.

Adoption and implementation of the original strict glycemic control guideline is feasible and safe in adult critically ill patients.

BACKGROUND: Three trials of tight glucose control (TGC) found clinical benefit of normalization of blood glucose levels in the intensive care unit (ICU). Implementation of TGC was imperfect in subsequent trials, since attained blood glucose levels (BGLs) never reached the targets as in the original trials of TGC. We investigated whether implementation of the TGC guideline as used in the original trials of TGC is feasible and safe. METHODS: In this study 3 ICUs adopted and implemented the TGC guideline as used in the original trials of TGC using a multifaceted practice change strategy; 3 ICUs that did not change their blood glucose control guideline served as controls. TGC was practiced by physicians and nurses during the first 12-month (period-2), thereafter exclusively by nurses (period-3). Blood glucose metrics 12-month before (period-1) and 24-month after implementation of the guideline were compared. RESULTS: The analysis included 1321 in period-1, 1169 and 1006 patients in period-2, and -3, respectively, in the intervention ICUs, and 3110 patients in the control ICUs. After implementation of the new TGC guideline, patients in intervention ICUs had lower median BGLs (105 [IQR: 85-130] mg/dL vs. 119 [99-150] mg/dL in period-1, P<0.001; and vs. 113 [95-141] mg/dL in control ICUs, P<0.001). The incidence of severe hypoglycemia initially increased, but again decreased when exclusively nurses practiced TGC, and was not associated with increased mortality or morbidity. CONCLUSIONS: Implementation of the original TGC guideline is feasible and safe. Our study suggests a learning effect over time.

Development and validation of PRE-DELIRIC (PREdiction of DELIRium in ICu patients) delirium prediction model for intensive care patients: observational multicentre study.

OBJECTIVES: To develop and validate a delirium prediction model for adult intensive care patients and determine its additional value compared with prediction by caregivers. DESIGN: Observational multicentre study. SETTING: Five intensive care units in the Netherlands (two university hospitals and three university affiliated teaching hospitals). PARTICIPANTS: 3056 intensive care patients aged 18 years or over. MAIN OUTCOME MEASURE: Development of delirium (defined as at least one positive delirium screening) during patients' stay in intensive care. RESULTS: The model was developed using 1613 consecutive intensive care patients in one hospital and temporally validated using 549 patients from the same hospital. For external validation, data were collected from 894 patients in four other hospitals. The prediction (PRE-DELIRIC) model contains 10 risk factors-age, APACHE-II score, admission group, coma, infection, metabolic acidosis, use of sedatives and morphine, urea concentration, and urgent admission. The model had an area under the receiver operating characteristics curve of 0.87 (95% confidence interval 0.85 to 0.89) and 0.86 after bootstrapping. Temporal validation and external validation resulted in areas under the curve of 0.89 (0.86 to 0.92) and 0.84 (0.82 to 0.87). The pooled area under the receiver operating characteristics curve (n=3056) was 0.85 (0.84 to 0.87). The area under the curve for nurses' and physicians' predictions (n=124) was significantly lower at 0.59 (0.49 to 0.70) for both. CONCLUSION: The PRE-DELIRIC model for intensive care patients consists of 10 risk factors that are readily available within 24 hours after intensive care admission and has a high predictive value. Clinical prediction by nurses and physicians performed significantly worse. The model allows for early prediction of delirium and initiation of preventive measures. Trial registration Clinical trials NCT00604773 (development study) and NCT00961389 (validation study).