Impact of reduced antibiotic treatment duration on antimicrobial resistance in critically ill patients in the randomized controlled SAPS-trial.

Background: In the previously reported SAPS trial (https://clinicaltrials.gov/ct2/show/NCT01139489), procalcitonin-guidance safely reduced the duration of antibiotic treatment in critically ill patients. We assessed the impact of shorter antibiotic treatment on antimicrobial resistance development in SAPS patients. Materials and methods: Cultures were assessed for the presence of multi-drug resistant (MDR) or highly resistant organisms (HRMO) and compared between PCT-guided and control patients. Baseline isolates from 30 days before to 5 days after randomization were compared with those from 5 to 30 days post-randomization. The primary endpoint was the incidence of new MDR/HRMO positive patients. Results: In total, 8,113 cultures with 96,515 antibiotic test results were evaluated for 439 and 482 patients randomized to the PCT and control groups, respectively. Disease severity at admission was similar for both groups. Median (IQR) durations of the first course of antibiotics were 6 days (4-10) and 7 days (5-11), respectively (p = 0.0001). Antibiotic-free days were 7 days (IQR 0-14) and 6 days (0-13; p = 0.05). Of all isolates assessed, 13% were MDR/HRMO positive and at baseline 186 (20%) patients were MDR/HMRO-positive. The incidence of new MDR/HRMO was 39 (8.9%) and 45 (9.3%) in PCT and control patients, respectively (p = 0.82). The time courses for MDR/HRMO development were also similar for both groups (p = 0.33). Conclusions: In the 921 randomized patients studied, the small but statistically significant reduction in antibiotic treatment in the PCT-group did not translate into a detectable change in antimicrobial resistance. Studies with larger differences in antibiotic treatment duration, larger study populations or populations with higher MDR/HRMO incidences might detect such differences.

A Quality Improvement Project to Support Post-Intensive Care Unit Patients with COVID-19: Structured Telephone Support.

BACKGROUND: More than 50% of intensive care unit (ICU) survivors suffer from long-lasting physical, psychosocial, and cognitive health impairments, also called "post-intensive care syndrome" (PICS). Intensive care admission during the COVID-19 pandemic was especially uncertain and stressful, both for patients and for their family. An additional risk of developing symptoms of PICS was feared in the absence of structural aftercare for the patient and family shortly after discharge from the hospital. The purpose of this quality improvement study was to identify PICS symptoms and to support post-intensive care patients and families in the transition from the hospital to the home. Therefore, we offered post-ICU patients and families structured telephone support (STS). METHODS: This was a quality improvement study during the 2019 COVID-19 pandemic. A project team developed and implemented a tool to structure telephone calls to identify and order symptoms according to the PICS framework and to give individual support based on this information. We supported post-ICU patients diagnosed with COVID-19 pneumonia and their family caregivers within four weeks after hospital discharge. The reported findings were both quantitative and qualitative. RESULTS: Forty-six post-ICU patients received structured telephone support and reported symptoms in at least one of the three domains of the PICS framework. More than half of the patients experienced a loss of strength or condition and fatigue. Cognitive and psychological impairments were reported less frequently. Family caregivers reported fewer impairments concerning fatigue and sleeping problems and expressed a need for a continuity of care. Based on the obtained information, the ICU nurse practitioners were able to check if individual care plans were optimal and clear and, if indicated, initiated disciplines to optimize further follow-up. CONCLUSIONS: The implementation of the STS tool gave insight in the impairments of post-ICU patients. Surprisingly, family caregivers expressed fewer impairments. Giving support early after hospital discharge in a structured way may contribute to providing guidance in the individual care plans and treatment of the early symptoms of PICS (-F).

Mid-regional proadrenomedullin, C-terminal proendothelin-1 values, and disease course are not different in critically ill SARS-CoV-2 pneumonia patients with obesity.

BACKGROUND/OBJECTIVES: Patients affected by obesity and Coronavirus disease 2019, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), appear to have a higher risk for intensive care (ICU) admission. A state of low-grade chronic inflammation in obesity has been suggested as one of the underlying mechanisms. We investigated whether obesity is associated with differences in new inflammatory biomarkers mid-regional proadrenomedullin (MR-proADM), C-terminal proendothelin-1 (CT-proET-1), and clinical outcomes in critically ill patients with SARS-CoV-2 pneumonia. SUBJECTS/METHODS: A total of 105 critically ill patients with SARS-CoV-2 pneumonia were divided in patients with obesity (body mass index (BMI) ≥ 30 kg/m2, n = 42) and patients without obesity (BMI < 30 kg/m2, n = 63) and studied in a retrospective observational cohort study. MR-proADM, CT-proET-1 concentrations, and conventional markers of white blood count (WBC), C-reactive protein (CRP), and procalcitonin (PCT) were collected during the first 7 days. RESULTS: BMI was 33.5 (32-36.1) and 26.2 (24.7-27.8) kg/m2 in the group with and without obesity. There were no significant differences in concentrations MR-proADM, CT-proET-1, WBC, CRP, and PCT at baseline and the next 6 days between patients with and without obesity. Only MR-proADM changed significantly over time (p = 0.039). Also, BMI did not correlate with inflammatory biomarkers (MR-proADM rho = 0.150, p = 0.125, CT-proET-1 rho = 0.179, p = 0.067, WBC rho = -0.044, p = 0.654, CRP rho = 0.057, p = 0.564, PCT rho = 0.022, p = 0.842). Finally, no significant differences in time on a ventilator, ICU length of stay, and 28-day mortality between patients with or without obesity were observed. CONCLUSIONS: In critically ill patients with confirmed SARS-CoV-2 pneumonia, obesity was not associated with differences in MR-proADM, and CT-proET-1, or impaired outcome. TRIAL REGISTRATION: Netherlands Trial Register, NL8460.

C-Terminal Proarginine Vasopressin is Associated with Disease Outcome and Mortality, but not with Delayed Cerebral Ischemia in Critically Ill Patients with an Aneurysmal Subarachnoid Hemorrhage: A Prospective Cohort Study.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is an important indication for intensive care unit admission and may lead to significant morbidity and mortality. We assessed the ability of C-terminal proarginine vasopressin (CT-proAVP) to predict disease outcome, mortality, and delayed cerebral ischemia (DCI) in critically ill patients with aSAH compared with the World Federation of Neurological Surgeons (WFNS) score and Acute Physiological and Chronic Health Evaluation IV (APACHE IV) model. METHODS: C-terminal proarginine vasopressin was collected on admission in this single-center, prospective, observational cohort study. The primary aim was to investigate the relationship between CT-proAVP and poor functional outcome at 1 year (Glasgow Outcome Scale score 1-3) in a multivariable logistic regression model adjusted for WFNS and APACHE IV scores. Secondary aims were mortality and DCI. The multivariable logistic regression model for DCI was also adjusted for the modified Fisher scale. RESULTS: In 100 patients, the median CT-proAVP level was 24.9 pmol/L (interquartile range 11.5-53.8); 45 patients had a poor 1-year functional outcome, 19 patients died within 30 days, 25 patients died within 1 year, and DCI occurred in 28 patients. Receiver operating characteristics curves revealed high accuracy for CT-proAVP to identify patients with poor 1-year functional outcome (area under the curve [AUC] 0.84, 95% confidence interval [CI] 0.77-0.92, p < 0.001), 30-day mortality (AUC 0.84, 95% CI 0.76-0.93, p < 0.001), and 1-year mortality (AUC 0.79, 95% CI 0.69-0.89, p < 0.001). CT-proAVP had a low AUC for identifying patients with DCI (AUC 0.67, 95% CI 0.55-0.79, p 0.008). CT-proAVP ≥ 24.9 pmo/L proved to be a significant predictor for poor 1-year functional outcome (odds ratio [OR] 8.04, 95% CI 2.97-21.75, p < 0.001), and CT-proAVP ≥ 29.1 pmol/L and ≥ 27.7 pmol/L were significant predictors for 30-day and 1-year mortality (OR 9.31, 95% CI 1.55-56.07, p 0.015 and OR 5.15, 95% CI 1.48-17.93, p 0.010) in multivariable models with WFNS and APACHE IV scores. CT-proAVP ≥ 29.5 pmol/L was not a significant predictor for DCI in a multivariable model adjusted for the modified Fisher scale (p = 0.061). CONCLUSIONS: C-terminal proarginine vasopressin was able to predict poor functional outcome and mortality in critically ill patients with aSAH. Its prognostic ability to predict DCI was low. TRIAL REGISTRATION: Nederlands Trial Register: NTR4118.

Intracerebral Hemorrhage and Thrombocytopenia After AstraZeneca COVID-19 Vaccine: Clinical and Diagnostic Challenges of Vaccine-Induced Thrombotic Thrombocytopenia.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a prothrombotic disorder, which has been described as a rare adverse effect of the adenoviral-vectored coronavirus disease 2019 (COVID-19) vaccines. The diagnosis is confirmed by the detection of anti-platelet factor 4 (PF4) antibodies by enzyme-linked immunosorbent assay (ELISA) or functional assay in individuals with the appropriate clinical history. Here, we report a case of a patient who presented with a severe intracerebral hemorrhage and thrombocytopenia 14 days after receiving the first dose of the Oxford-AstraZeneca COVID-19 vaccine, with negative PF4/heparin antibodies tested with ELISA, but positive heparin-induced platelet activation assay (HIPAA).

Endothelium-associated biomarkers mid-regional proadrenomedullin and C-terminal proendothelin-1 have good ability to predict 28-day mortality in critically ill patients with SARS-CoV-2 pneumonia: A prospective cohort study.

PURPOSE: We assessed the ability of mid-regional proadrenomedullin (MR-proADM) and C-terminal proendothelin-1 (CT-proET-1) to predict 28-day mortality in critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia. METHODS: Biomarkers were collected during the first seven days in this prospective observational cohort study. We investigated the relationship between biomarkers and mortality in a multivariable Cox regression model adjusted for age and SOFA score. RESULTS: In 105 critically ill patients with confirmed SARS-CoV-2 pneumonia 28-day mortality was 28.6%. MR-proADM and CT-proET-1 were significantly higher in 28-day non-survivors at baseline and over time. ROC curves revealed high accuracy to identify non-survivors for baseline MR-proADM and CT-proET-1, AUC 0.84, (95% CI 0.76-0.92), p < 0.001 and 0.79, (95% CI 0.69-0.89), p < 0.001, respectively. The AUC for prediction of 28-day mortality for MR-proADM and CT-proET-1 remained high over time. MR-proADM ≥1.57 nmol/L and CT-proET-1 ≥ 111 pmol/L at baseline were significant predictors for 28-day mortality (HR 6.80, 95% CI 3.12-14.84, p < 0.001 and HR 3.72, 95% CI 1.71-8.08, p 0.01). CONCLUSION: Baseline and serial MR-proADM and CT-proET-1 had good ability to predict 28-day mortality in critically ill patients with SARS-CoV-2 pneumonia. TRIAL REGISTRATION: NEDERLANDS TRIAL REGISTER, NL8460.

Obesity May Not Be Associated with 28-Day Mortality, Duration of Invasive Mechanical Ventilation and Length of Intensive Care Unit and Hospital Stay in Critically Ill Patients with Severe Acute Respiratory Syndrome Coronavirus-2: A Retrospective Cohort Study.

Background and Objectives: The aim of this study was to investigate the association between obesity and 28-day mortality, duration of invasive mechanical ventilation and length of stay at the Intensive Care Unit (ICU) and hospital in patients admitted to the ICU for SARS-CoV-2 pneumonia. Materials and Methods: This was a retrospective observational cohort study in patients admitted to the ICU for SARS-CoV-2 pneumonia, in a single Dutch center. The association between obesity (body mass index > 30 kg/m2) and 28-day mortality, duration of invasive mechanical ventilation and length of ICU and hospital stay was investigated. Results: In 121 critically ill patients, pneumonia due to SARS-CoV-2 was confirmed by RT-PCR. Forty-eight patients had obesity (33.5%). The 28-day all-cause mortality was 28.1%. Patients with obesity had no significant difference in 28-day survival in Kaplan-Meier curves (log rank p 0.545) compared with patients without obesity. Obesity made no significant contribution in a multivariate Cox regression model for prediction of 28-day mortality (p = 0.124), but age and the Sequential Organ Failure Assessment (SOFA) score were significant independent factors (p < 0.001 and 0.002, respectively). No statistically significant correlation was observed between obesity and duration of invasive mechanical ventilation and length of ICU and hospital stay. Conclusion: One-third of the patients admitted to the ICU for SARS-CoV-2 pneumonia had obesity. The present study showed no relationship between obesity and 28-day mortality, duration of invasive mechanical ventilation, ICU and hospital length of stay. Further studies are needed to substantiate these findings.

Mid-Regional Proadrenomedullin and Mid-Regional Proatrial Natriuretic Peptide Clearance Predicts Poor Outcomes Better Than Single Baseline Measurements in Critically Ill Patients With Pneumonia: A Retrospective Cohort Study.

Background We assessed the ability of baseline and serial measurements of mid-regional proadrenomedullin (MR-proADM) and mid-regional proatrial natriuretic peptide (MR-proANP) to predict 28-day mortality in critically ill patients with pneumonia compared with Acute Physiological and Chronic Health Evaluation IV (APACHE IV) model and Sequential Organ Failure Assessment (SOFA) score. Methodology Biomarkers were collected for the first five days in this retrospective observational cohort study. Biomarker clearance (as a percentage) was presented as biomarker decline in five days. We investigated the relationship between biomarkers and mortality in a multivariable Cox regression model. APACHE IV and SOFA were calculated after 24 hours from intensive care unit admission. Results In 153 critically ill patients with pneumonia, 28-day mortality was 26.8%. Values of baseline MR-proADM, MR-proANP, and APACHE IV were significantly higher in 28-day nonsurvivors, but not significantly different for SOFA score. Baseline MR-proADM and MR-proANP, APACHE IV, and SOFA had a low area under the curve in receiver operating characteristics (ROC) curves. No optimal cut-off points could be calculated. Biomarkers and severity scores were divided into tertiles. The highest tertiles baseline MR-proADM and MR-proANP were not significant predictors for 28-day mortality in a multivariable model with age and APACHE IV. SOFA was not a significant predictor in univariable analysis. Clearances of MR-proADM and MR-proANP were significantly higher in 28-day survivors. MR-proADM and MR-proANP clearances had similar low accuracy to identify nonsurvivors in ROC curves and were divided into tertiles. Low clearances of MR-proADM and MR-proANP (first tertiles) were significant predictors for 28-day mortality (hazard ratio [HR]: 2.38; 95% confidence interval [CI]: 1.21-4.70; p = 0.013 and HR: 2.27; 95% CI: 1.16-4.46; p = 0.017) in a model with age and APACHE IV. Conclusions MR-proADM and MR-proANP clearance performed better in predicting 28-day mortality in a model with age and APACHE IV compared with single baseline measurements in a mixed population of critically ill with pneumonia.

Duration of antibiotic treatment using procalcitonin-guided treatment algorithms in older patients: a patient-level meta-analysis from randomized controlled trials.

BACKGROUND: Older patients have a less pronounced immune response to infection, which may also influence infection biomarkers. There is currently insufficient data regarding clinical effects of procalcitonin (PCT) to guide antibiotic treatment in older patients. OBJECTIVE AND DESIGN: We performed an individual patient data meta-analysis to investigate the association of age on effects of PCT-guided antibiotic stewardship regarding antibiotic use and outcome. SUBJECTS AND METHODS: We had access to 9,421 individual infection patients from 28 randomized controlled trials comparing PCT-guided antibiotic therapy (intervention group) or standard care. We stratified patients according to age in four groups (<75 years [n = 7,079], 75-80 years [n = 1,034], 81-85 years [n = 803] and >85 years [n = 505]). The primary endpoint was the duration of antibiotic treatment and the secondary endpoints were 30-day mortality and length of stay. RESULTS: Compared to control patients, mean duration of antibiotic therapy in PCT-guided patients was significantly reduced by 24, 22, 26 and 24% in the four age groups corresponding to adjusted differences in antibiotic days of -1.99 (95% confidence interval [CI] -2.36 to -1.62), -1.98 (95% CI -2.94 to -1.02), -2.20 (95% CI -3.15 to -1.25) and - 2.10 (95% CI -3.29 to -0.91) with no differences among age groups. There was no increase in the risk for mortality in any of the age groups. Effects were similar in subgroups by infection type, blood culture result and clinical setting (P interaction >0.05). CONCLUSIONS: This large individual patient data meta-analysis confirms that, similar to younger patients, PCT-guided antibiotic treatment in older patients is associated with significantly reduced antibiotic exposures and no increase in mortality.

Characteristics and Risk Factors Associated With Mortality in Critically Ill Patients With COVID-19.

Purpose To describe clinical characteristics and outcomes of ICU patients with COVID-19 and to investigate differences between survivors and non-survivors. Methods Demographics, symptoms, laboratory values, comorbidities and outcomes were extracted retrospectively from the medical records of ICU patients with confirmed COVID-19 pneumonia from the Elisabeth-TweeSteden Hospital in Tilburg, the Netherlands from March until June 2020. Primary outcome was 28-day mortality and secondary outcomes were differences between survivors and non-survivors. Results Between March 1 and June 4, 2020, 114 patients with COVID-19 were admitted to the ICU. There were 83 (72.8%) survivors and 31 (27.2%) non-survivors. Non-survivors were significantly older (72.0 years [interquartile range, IQR 67.0-76.0] versus 65.0 years [IQR 58.0-73.0], P = 0.002), had a significantly higher Acute Physiology And Chronic Health Evaluation (APACHE) score (54 [IQR 45-72] versus 43 [IQR 36-53], P < 0.001) and Sequential Organ Failure Assessment (SOFA) score (7 [IQR 4-7] versus 5 [IQR 3-6], P = 004). cTnT values were significantly higher in non-survivors due to more myocarditis (83.9% versus 40.8%, P < 0.001). A multivariate Cox regression model revealed SOFA score (hazard ratio, HR 1.337, 95% CI 1.131-1.582, P = 0.001) to be an independent predictor of 28-day mortality. Conclusion We demonstrated a 28-day mortality rate of 27.2% in our cohort. These patients were older and presented with a higher severity of illness and more organ failure.

Posaconazole for prevention of invasive pulmonary aspergillosis in critically ill influenza patients (POSA-FLU): a randomised, open-label, proof-of-concept trial.

PURPOSE: Influenza-associated pulmonary aspergillosis (IAPA) is a frequent complication in critically ill influenza patients, associated with significant mortality. We investigated whether antifungal prophylaxis reduces the incidence of IAPA. METHODS: We compared 7 days of intravenous posaconazole (POS) prophylaxis with no prophylaxis (standard-of-care only, SOC) in a randomised, open-label, proof-of-concept trial in patients admitted to an intensive care unit (ICU) with respiratory failure due to influenza (ClinicalTrials.gov, NCT03378479). Adult patients with PCR-confirmed influenza were block randomised (1:1) within 10 days of symptoms onset and 48 h of ICU admission. The primary endpoint was the incidence of IAPA during ICU stay in patients who did not have IAPA within 48 h of ICU admission (modified intention-to-treat (MITT) population). RESULTS: Eighty-eight critically ill influenza patients were randomly allocated to POS or SOC. IAPA occurred in 21 cases (24%), the majority of which (71%, 15/21) were diagnosed within 48 h of ICU admission, excluding them from the MITT population. The incidence of IAPA was not significantly reduced in the POS arm (5.4%, 2/37) compared with SOC (11.1%, 4/36; between-group difference 5.7%; 95% CI - 10.8 to 21.7; p = 0.32). ICU mortality of early IAPA was high (53%), despite rapid antifungal treatment. CONCLUSION: The higher than expected incidence of early IAPA precludes any definite conclusion on POS prophylaxis. High mortality of early IAPA, despite timely antifungal therapy, indicates that alternative management strategies are required. After 48 h, still 11% of patients developed IAPA. As these could benefit from prophylaxis, differentiated strategies are likely needed to manage IAPA in the ICU.

Association of kidney function with effectiveness of procalcitonin-guided antibiotic treatment: a patient-level meta-analysis from randomized controlled trials.

Objectives: Patients with impaired kidney function have a significantly slower decrease of procalcitonin (PCT) levels during infection. Our aim was to study PCT-guided antibiotic stewardship and clinical outcomes in patients with impairments of kidney function as assessed by creatinine levels measured upon hospital admission. Methods: We pooled and analyzed individual data from 15 randomized controlled trials who were randomly assigned to receive antibiotic therapy based on a PCT-algorithms or based on standard of care. We stratified patients on the initial glomerular filtration rate (GFR, ml/min/1.73 m2) in three groups (GFR >90 [chronic kidney disease; CKD 1], GFR 15-89 [CKD 2-4] and GFR<15 [CKD 5]). The main efficacy and safety endpoints were duration of antibiotic treatment and 30-day mortality. Results: Mean duration of antibiotic treatment was significantly shorter in PCT-guided (n=2,492) compared to control patients (n=2,510) (9.5-7.6 days; adjusted difference in days -2.01 [95% CI, -2.45 to -1.58]). CKD 5 patients had overall longer treatment durations, but a 2.5-day reduction in treatment duration was still found in patients receiving in PCT-guided care (11.3 vs. 8.6 days [95% CI -3.59 to -1.40]). There were 397 deaths in 2,492 PCT-group patients (15.9%) compared to 460 deaths in 2,510 control patients (18.3%) (adjusted odds ratio, 0.88 [95% CI 0.78 to 0.98)]. Effects of PCT-guidance on antibiotic treatment duration and mortality were similar in subgroups stratified by infection type and clinical setting (p interaction >0.05). Conclusions: This individual patient data meta-analysis confirms that the use of PCT in patients with impaired kidney function, as assessed by admission creatinine levels, is associated with shorter antibiotic courses and lower mortality rates.

[The first 100 COVID-19 patients admitted to the Elisabeth-Tweesteden Hospital, Tilburg, The Netherlands]. / De eerste honderd opgenomen COVID-19-patiënten in het Elisabeth-Tweesteden Ziekenhuis.

Here we describe the characteristics of the first 100 laboratory confirmed COVID-19 patients admitted to the Elisabeth-Tweesteden Hospital (Tilburg, The Netherlands). The median age was 72 years, 67% was male, approximately 80% had co-morbidity, approximately 50% of which consisted of hypertension, cardiac and or pulmonary conditions and 25% diabetes. At admission 61% of patients had fever and about 50% presented at day 6 or more after onset of symptoms. At the time of writing 38 patients were discharged, 19 admitted to the intensive care unit (ICU) and 20 patients had died. The median age of ICU patients was 67 years and 63% had co-morbidity. The median time to discharge or to death was 6 and 5.5 days, respectively.

Diagnostic Accuracy of Procalcitonin and C-reactive Protein Is Insufficient to Predict Proven Infection: A Retrospective Cohort Study in Critically Ill Patients Fulfilling the Sepsis-3 Criteria.

BACKGROUND: New Sepsis-3 definitions facilitate early recognition of patients with sepsis. In this study we investigated whether a single initial determination of procalcitonin (PCT) or C-reactive protein (CRP) in plasma can predict proven sepsis in Sepsis-3 criteria-positive critically ill patients. We also investigated whether a decline in serial PCT or CRP can predict outcome in 28-day mortality. METHODS: Patients, ≥18 years of age, at the intensive care unit with a suspected infection, a Sequential Organ Failure Assessment (SOFA) score of ≥2 points, and an index test PCT and CRP at admission were selected from a prospectively collected cohort. PCT and CRP were studied retrospectively with the Mann-Whitney U-test and ROC analysis. RESULTS: In total, 157 patients were selected; 63 of the 157 had proven sepsis, and sepsis could not be detected in 94 of the 157. Neither a single PCT nor CRP at admission was able to discriminate proven sepsis from nonproven sepsis (PCT, 1.8 µg/L and 1.5 µg/L, respectively, P = 0.25; CRP, 198 mg/L and 186 mg/L, respectively, P = 0.53). Area under the curve for both PCT and CRP for detecting proven sepsis was low (0.55 and 0.53). Furthermore, neither a decline from baseline to day 5 PCT nor CRP could predict 28-day mortality (PCT, 50% vs 46%, P = 0.83; CRP, 30% vs 40%, P = 0.51). CONCLUSION: PCT and CRP at admission were not able to discern patients with proven sepsis in Sepsis-3 criteria-positive critically ill patients. A decline of PCT and CRP in 5 days was not able to predict 28-day mortality.

[A man with subcutaneous emphysema]. / Een man met acuut subcutaan emfyseem.

After insertion of a nasal oxygen catheter, a 65-year-old man developed severe subcutaneous emphysema of the face and neck. The catheter damaged the mucosa of the left inferior nasal concha. Oxygen was blown into the subcutis. Emergency intubation was needed to secure the airway. The patient recovered within 24 hours.

Cost-effectiveness of procalcitonin testing to guide antibiotic treatment duration in critically ill patients: results from a randomised controlled multicentre trial in the Netherlands.

BACKGROUND: Procalcitonin (PCT) testing can help in safely reducing antibiotic treatment duration in intensive care patients with sepsis. However, the cost-effectiveness of such PCT guidance is not yet known. METHODS: A trial-based analysis was performed to estimate the cost-effectiveness of PCT guidance compared with standard of care (without PCT guidance). Patient-level data were used from the SAPS trial in which 1546 patients were randomised. This trial was performed in the Netherlands, which is a country with, on average, low antibiotic use and a short duration of hospital stay. As quality of life among sepsis survivors was not measured during the SAPS, this was derived from a Dutch follow-up study. Outcome measures were (1) incremental direct hospital cost and (2) incremental cost per quality-adjusted life year (QALY) gained from a healthcare perspective over a one-year time horizon. Uncertainty in outcomes was assessed with bootstrapping. RESULTS: Mean in-hospital costs were €46,081/patient in the PCT group compared with €46,146/patient with standard of care (i.e. - €65 (95% CI - €6314 to €6107); - 0.1%). The duration of the first course of antibiotic treatment was lower in the PCT group with 6.9 vs. 8.2 days (i.e. - 1.2 days (95% CI - 1.9 to - 0.4), - 14.8%). This was accompanied by lower in-hospital mortality of 21.8% vs. 29.8% (absolute decrease 7.9% (95% CI - 13.9% to - 1.8%), relative decrease 26.6%), resulting in an increase in mean QALYs/patient from 0.47 to 0.52 (i.e. + 0.05 (95% CI 0.00 to 0.10); + 10.1%). However, owing to high costs among sepsis survivors, healthcare costs over a one-year time horizon were €73,665/patient in the PCT group compared with €70,961/patient with standard of care (i.e. + €2704 (95% CI - €4495 to €10,005), + 3.8%), resulting in an incremental cost-effectiveness ratio of €57,402/QALY gained. Within this time frame, the probability of PCT guidance being cost-effective was 64% at a willingness-to-pay threshold of €80,000/QALY. CONCLUSIONS: Although the impact of PCT guidance on total healthcare-related costs during the initial hospitalisation episode is likely negligible, the lower in-hospital mortality may lead to a non-significant increase in costs over a one-year time horizon. However, since uncertainty remains, it is recommended to investigate the long-term cost-effectiveness of PCT guidance, from a societal perspective, in different countries and settings.

Effect of procalcitonin-guided antibiotic treatment on clinical outcomes in intensive care unit patients with infection and sepsis patients: a patient-level meta-analysis of randomized trials.

BACKGROUND: The clinical utility of serum procalcitonin levels in guiding antibiotic treatment decisions in patients with sepsis remains unclear. This patient-level meta-analysis based on 11 randomized trials investigates the impact of procalcitonin-guided antibiotic therapy on mortality in intensive care unit (ICU) patients with infection, both overall and stratified according to sepsis definition, severity, and type of infection. METHODS: For this meta-analysis focusing on procalcitonin-guided antibiotic management in critically ill patients with sepsis of any type, in February 2018 we updated the database of a previous individual patient data meta-analysis which was limited to patients with respiratory infections only. We used individual patient data from 11 trials that randomly assigned patients to receive antibiotics based on procalcitonin levels (the "procalcitonin-guided" group) or the current standard of care (the "controls"). The primary endpoint was mortality within 30 days. Secondary endpoints were duration of antibiotic treatment and length of stay. RESULTS: Mortality in the 2252 procalcitonin-guided patients was significantly lower compared with the 2230 control group patients (21.1% vs 23.7%; adjusted odds ratio 0.89, 95% confidence interval (CI) 0.8 to 0.99; p = 0.03). These effects on mortality persisted in a subgroup of patients meeting the sepsis 3 definition and based on the severity of sepsis (assessed on the basis of the Sequential Organ Failure Assessment (SOFA) score, occurrence of septic shock or renal failure, and need for vasopressor or ventilatory support) and on the type of infection (respiratory, urinary tract, abdominal, skin, or central nervous system), with interaction for each analysis being > 0.05. Procalcitonin guidance also facilitated earlier discontinuation of antibiotics, with a reduction in treatment duration (9.3 vs 10.4 days; adjusted coefficient -1.19 days, 95% CI -1.73 to -0.66; p <  0.001). CONCLUSION: Procalcitonin-guided antibiotic treatment in ICU patients with infection and sepsis patients results in improved survival and lower antibiotic treatment duration.

Analysis of the level of clinical skills of physician assistants tested with simulated intensive care patients.

RATIONALE, AIMS, AND OBJECTIVES: Since adequate staffing in intensive care units (ICUs) is an increasing problem worldwide, we investigated whether physician assistants (PAs) are able to substitute medical residents (MR) in ICUs with at least the same quality of clinical skills. In this study, we analysed the level of clinical skills of PAs in direct comparison with those who traditionally performed these tasks, ie, MR with 6 to 24 months of work experience in the ICU. METHOD: Physician assistants and MRs in the ICUs were observed on their clinical skills by means of a simulated ICU comprising 2 scenarios on a human patient simulator with typical ICU cases. The level of clinical skills of PAs and MRs was videotaped and scored with predefined checklists by 2 independent intensivists per scenario. Percentage of the total score was calculated, and means were compared by Student t test. RESULTS: A total of 11 PAs and 10 MRs participated in the study. Physician assistants and MRs scored equal (PA 66% ± 13% vs MR 68% ± 9%, P = .86) on their clinical performance in the simulated ICU setting. CONCLUSION: This study showed equal performance of PAs and MRs on clinical skills in the simulated ICU setting.