Pulmonary levels of biomarkers for inflammation and lung injury in protective versus conventional one-lung ventilation for oesophagectomy: A randomised clinical trial.

BACKGROUND: It is uncertain whether protective ventilation reduces ventilation-induced pulmonary inflammation and injury during one-lung ventilation. OBJECTIVE: To compare intra-operative protective ventilation with conventional during oesophagectomy with respect to pulmonary levels of biomarkers for inflammation and lung injury. DESIGN: Randomised clinical trial. SETTING: Tertiary centre for oesophageal diseases. PATIENTS: Twenty-nine patients scheduled for one-lung ventilation during oesophagectomy. INTERVENTIONS: Low tidal volume (VT) of 6 ml kg predicted body weight (pbw) during two-lung ventilation and 3 ml kgpbw during one-lung ventilation with 5 cmH2O positive end expired pressure versus intermediate VT of 10 ml kgpbw during two-lung ventilation and 5 ml kgpbw body weight during one-lung ventilation with no positive end-expiratory pressure. OUTCOME MEASURES: The primary outcome was the change in bronchoalveolar lavage (BAL) levels of preselected biomarkers for inflammation (TNF-α, IL-6 and IL-8) and lung injury (soluble Receptor for Advanced Glycation End-products, surfactant protein-D, Clara Cell protein 16 and Krebs von den Lungen 6), from start to end of ventilation. RESULTS: Median [IQR] VT in the protective ventilation group (n = 13) was 6.0 [5.7 to 7.8] and 3.1 [3.0 to 3.6] ml kgpbw during two and one-lung ventilation; VT in the conventional ventilation group (n = 16) was 9.8 [7.0 to 10.1] and 5.2 [5.0 to 5.5] ml kgpbw during two and one-lung ventilation. BAL levels of biomarkers for inflammation increased from start to end of ventilation in both groups; levels of soluble Receptor for Advanced Glycation End-products, Clara Cell protein 16 and Krebs von den Lungen 6 did not change, while levels of surfactant protein-D decreased. Changes in BAL biomarkers levels were not significantly different between the two ventilation strategies. CONCLUSION: Intra-operative protective ventilation compared with conventional ventilation does not affect changes in pulmonary levels of biomarkers for inflammation and lung injury in patients undergoing one-lung ventilation for oesophagectomy. TRIAL REGISTRATION: The 'Low versus Conventional tidal volumes during one-lung ventilation for minimally invasive oesophagectomy trial' (LoCo) was registered at the Netherlands Trial Register (study identifier NTR 4391).

Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial.

BACKGROUND: In critically ill patients, antibiotic therapy is of great importance but long duration of treatment is associated with the development of antimicrobial resistance. Procalcitonin is a marker used to guide antibacterial therapy and reduce its duration, but data about safety of this reduction are scarce. We assessed the efficacy and safety of procalcitonin-guided antibiotic treatment in patients in intensive care units (ICUs) in a health-care system with a comparatively low use of antibiotics. METHODS: We did a prospective, multicentre, randomised, controlled, open-label intervention trial in 15 hospitals in the Netherlands. Critically ill patients aged at least 18 years, admitted to the ICU, and who received their first dose of antibiotics no longer than 24 h before inclusion in the study for an assumed or proven infection were eligible to participate. Patients who received antibiotics for presumed infection were randomly assigned (1:1), using a computer-generated list, and stratified (according to treatment centre, whether infection was acquired before or during ICU stay, and dependent on severity of infection [ie, sepsis, severe sepsis, or septic shock]) to receive either procalcitonin-guided or standard-of-care antibiotic discontinuation. Both patients and investigators were aware of group assignment. In the procalcitonin-guided group, a non-binding advice to discontinue antibiotics was provided if procalcitonin concentration had decreased by 80% or more of its peak value or to 0·5 µg/L or lower. In the standard-of-care group, patients were treated according to local antibiotic protocols. Primary endpoints were antibiotic daily defined doses and duration of antibiotic treatment. All analyses were done by intention to treat. Mortality analyses were completed for all patients (intention to treat) and for patients in whom antibiotics were stopped while being on the ICU (per-protocol analysis). Safety endpoints were reinstitution of antibiotics and recurrent inflammation measured by C-reactive protein concentrations and they were measured in the population adhering to the stopping rules (per-protocol analysis). The study is registered with ClinicalTrials.gov, number NCT01139489, and was completed in August, 2014. FINDINGS: Between Sept 18, 2009, and July 1, 2013, 1575 of the 4507 patients assessed for eligibility were randomly assigned to the procalcitonin-guided group (761) or to standard-of-care (785). In 538 patients (71%) in the procalcitonin-guided group antibiotics were discontinued in the ICU. Median consumption of antibiotics was 7·5 daily defined doses (IQR 4·0-12·7) in the procalcitonin-guided group versus 9·3 daily defined doses (5·0-16·6) in the standard-of-care group (between-group absolute difference 2·69, 95% CI 1·26-4·12, p<0·0001). Median duration of treatment was 5 days (3-9) in the procalcitonin-guided group and 7 days (4-11) in the standard-of-care group (between-group absolute difference 1·22, 0·65-1·78, p<0·0001). Mortality at 28 days was 149 (20%) of 761 patients in the procalcitonin-guided group and 196 (25%) of 785 patients in the standard-of-care group (between-group absolute difference 5·4%, 95% CI 1·2-9·5, p=0·0122) according to the intention-to-treat analysis, and 107 (20%) of 538 patients in the procalcitonin-guided group versus 121 (27%) of 457 patients in the standard-of-care group (between-group absolute difference 6·6%, 1·3-11·9, p=0·0154) in the per-protocol analysis. 1-year mortality in the per-protocol analysis was 191 (36%) of 538 patients in the procalcitonin-guided and 196 (43%) of 457 patients in the standard-of-care groups (between-group absolute difference 7·4, 1·3-13·8, p=0·0188). INTERPRETATION: Procalcitonin guidance stimulates reduction of duration of treatment and daily defined doses in critically ill patients with a presumed bacterial infection. This reduction was associated with a significant decrease in mortality. Procalcitonin concentrations might help physicians in deciding whether or not the presumed infection is truly bacterial, leading to more adequate diagnosis and treatment, the cornerstones of antibiotic stewardship. FUNDING: Thermo Fisher Scientific.

Current Use of Pain Scores in Dutch Intensive Care Units: A Postal Survey in the Netherlands.

BACKGROUND: Pain is a common problem for critically ill patients treated in the intensive care unit (ICU) and can have serious consequences. For this reason, the appropriate recognition and treatment of pain is of extreme importance. However, pain assessment in critically ill patients can be challenging because these patients are often unable to self-report. To identify attitudes and practices regarding the assessment and management of pain in ICU patients unable to self-report, we surveyed all adult ICUs in the Netherlands. METHODS: A multicenter, exploratory survey was sent by mail to all adult ICUs in the Netherlands. RESULTS: Eighty-four of 107 ICUs returned the questionnaire for a response rate of 79%. In patients able to self-report, 94% (n = 79; 95% confidence interval [CI], 86.7%-98%) of the ICUs used a standardized pain score. Visual Analog Scale and Numerical Rating Scale were used in 57% (n = 48; 99.3% CI, 41%-72%) and 48% (n = 40; 99.3% CI, 33%-64%), respectively. Nonteaching hospitals used pain assessment tools more often than teaching hospitals (P = 0.012). In patients not able to self-report, pain assessment tools were used in 19% (n = 16) of the ICUs. In the ICUs that used behaviorally based scoring systems, the Critical Care Pain Observation Tool and Behavioral Pain Scale (BPS) were used in 6% (n = 5; 99.5% CI, 1.1%-17%) and 5% (n = 4; 99.5% CI, 0.1%-15%), respectively. Among Dutch nurses, nursing opinion was considered the gold standard assessment in 36% (n = 30; 98.8% CI, 23%-50%) of the respondents, even when a patient was able to self-report and pain scales were used. In patients unable to self-report, nurses judged themselves to be more accurate than a behavioral pain assessment tool in 98% (n = 82; 98.8% CI, 89.7%-99.9%) of the patients. CONCLUSIONS: In the Netherlands, most ICUs used a standardized pain score in patients able to self-report. Nonteaching hospitals used pain assessment tools more often than teaching hospitals. In patients unable to self-report, pain is not routinely measured with a validated behavioral pain assessment tool. Almost all nurses in our survey felt that their assessment of patient pain was more accurate than behavioral pain assessment tools in patients unable to self-report. More research is needed to identify factors preventing more widespread acceptance of validated behavioral pain scores in patients unable to self-report.

Perception by family members and ICU staff of the quality of dying and death in the ICU: a prospective multicenter study in The Netherlands.

OBJECTIVE: Admission to the ICU is a major event in a patient's life and also for family members. We tried to elucidate how family members and ICU caregivers experience the dying process of their patients. METHODS: The prospective study took place in three Dutch ICUs. Patients who had stayed . 48 h and died in the ICU were eligible. The Quality of Dying and Death (QODD) questionnaire was used, with addition of items pertaining to the patient's autonomy. Values indicate median and interquartile range. RESULTS: We included 100 consecutive patients. ICU stay before death was 8 (3-16) days. APACHE (Acute Physiology and Chronic Health Evaluation) II score at admission was 24 (19-31). Family response rate was 89%. Families were satisfied with overall QODD (score, 8 [7-9]) and felt supported by the ICU caregivers (8 [7-9]). Pain control was scored lower by family members (8 [5.75- 8.25]) than by nurses and physicians (9 [8-10], P 5 .024) Almost always, physicians discussed the patient's end-of-life wishes with family members, although families rated the quality of the discussion lower (7 [5.5-8.5]) than physicians (9 [6.5-10]) ( P 5 .045). The majority of the families (89%) felt included in the decision-making process. More than one-half of the family members (57%) believed that the physician made the fi nal decision alone after giving information, whereas 36.8% believed they had participated in making the decision. Family members rated the QODD questionnaire as difficult (6 [5-8]), and several items were not answered by a majority of family members. CONCLUSIONS: Quality of dying and death is generally perceived to be good by family members and caregivers of patients who die in Dutch ICUs. There is a need for modification of the QODD questionnaire for the European ICU population.