High-risk Intensive Care Unit Patients Research Articles

Is the T2MR Candida Panel a suitable alternative to the SeptiFast for the rapid diagnosis of candidemia in routine clinical practice?

ObjectivesThe diagnosis of invasive Candida infection remains challenging because of tests with slow turnaround times or mediocre performance. T2magnetic resonance imaging is a new diagnostic tool. We investigated the diagnostic accuracy of the T2Candida panel (T2) in comparison with blood culture (BC) and the SeptiFast (SF) for the detection of five different Candida species among high-risk intensive care unit patients with suspected candidemia. MethodsWe analysed blood samples collected from patients with suspected candidemia (177 samples from 138 patients) from August 2018 to April 2020. Blood samples were collected and analysed concurrently by BC, SF, and T2Candida. Subsequently, based on clinical and microbiological findings, patient samples were assigned to specific risk categories (proven, probable, and no candidemia). ResultsTwenty-two samples from 17 patients were classified as proven candidemia, and 15 samples from 14 patients were classified as probable candidemia. A sensitivity of 68.2% (95% CI, 45–86%) was observed for the BC and the SF, and a sensitivity of 63.6% (95% CI, 41–83%) was observed for the T2 when only cases with proven candidemia were evaluated. For proven and probable candidemia, the sensitivity was 40.5% (95% CI, 23–58%) for BC, 81.1% (95% CI, 65–92%) for SF, and 73.0% (95% CI, 56–86%) for T2. DiscussionThe diagnostic performance of SF and T2 was similar. For samples with proven/probable candidemia, SF and T2 had a higher sensitivity compared to BC. Used in conjunction with other diagnostic methods, T2 can replace the no longer available SF for the diagnosis of candidemia, enabling the timely initiation of targeted antifungal therapy.

Calibration of the PREdiction of DELIRium in ICu Patients (PRE-DELIRIC) Score in a Cohort of Critically Ill Patients: A Retrospective Cohort Study.

To predict delirium in intensive care unit (ICU) patients, the Prediction of Delirium in ICU Patients (PRE-DELIRIC) score may be used. This model may help nurses to predict delirium in high-risk ICU patients. The aims of this study were to externally validate the PRE-DELIRIC model and to identify predictive factors and outcomes for ICU delirium. All patients underwent delirium risk assessment by the PRE-DELIRIC model at admission. We used the Intensive Care Delirium Screening Check List to identify patients with delirium. The receiver operating characteristic curve measured discrimination capacity among patients with or without ICU delirium. Calibration ability was determined by slope and intercept. The prevalence of ICU delirium was 55.8%. Discrimination capacity (Intensive Care Delirium Screening Check List score ≥4) expressed by the area under the receiver operating characteristic curve was 0.81 (95% confidence interval, 0.75-0.88), whereas sensitivity was 91.3% and specificity was 64.4%. The best cut-off was 27%, obtained by the max Youden index. Calibration of the model was adequate, with a slope of 1.03 and intercept of 8.14. The onset of ICU delirium was associated with an increase in ICU length of stay (P < .0001), higher ICU mortality (P = .008), increased duration of mechanical ventilation (P < .0001), and more prolonged respiratory weaning (P < .0001) compared with patients without delirium. The PRE-DELIRIC score is a sensitive measure that may be useful in early detection of patients at high risk for developing delirium. The baseline PRE-DELIRIC score could be useful to trigger use of standardized protocols, including nonpharmacologic interventions.

Detection of Candida DNA in peritoneal fluids by PCR assay optimizing the diagnosis and treatment for intra-abdominal candidiasis in high-risk ICU patients: A prospective cohort study.

Intra-abdominal candidiasis (IAC) is the predominant type of invasive candidiasis with high mortality in critically ill patients. This study aimed to investigate whether the polymerase chain reaction (PCR) assay for detecting Candida DNA in peritoneal fluids (PF) is useful in diagnosing and management of IAC in high-risk patients in intensive care unit (ICU). A prospective single-center cohort study of surgical patients at high risk for IAC was conducted in the ICU. PF was collected from the abdominal drainage tubes (within 24 h) or by percutaneous puncture. Direct PF smear microscopy, PF culture, blood culture, and serum (1-3)-β-D-glucan were performed in all patients. For Candida PCR assay, the ITS1/ITS4 primers that targeted the ITS1-5.8 s-ITS2 regions were used for PCR, and sequencing analysis was used to identify the pathogen at the species level. IAC was defined according to the 2013 European consensus criteria. Among 83 patients at high risk for IAC, the IAC criteria were present in 17 (20.5%). The sensitivity and specificity of the Candida PCR assay were 64.7 and 89.4%, respectively, and the area under the receiver operating characteristic curve was 0.77 (95% CI: 0.63-0.91). In this cohort, the positive predictive value and negative predictive value were 90.8% (95% CI: 80.3-96.2%) and 61.1% (95% CI: 36.1-81.7%), respectively. Diagnostic consistency was moderate (kappa 0.529, p < 0.001) according to the 2013 European consensus criteria. Detection of Candida DNA in PF using PCR can be considered an adjunct to existing routine diagnostic tools which may optimize the diagnosis and antifungal treatment of IAC in high-risk patients in the ICU.

Percutaneous dilatational tracheotomy in high-risk ICU patients

BackgroundPercutaneous dilatational tracheotomy (PDT) has become an established procedure in intensive care units (ICU). However, the safety of this method has been under debate given the growing number of critically ill patients with high bleeding risk receiving anticoagulation, dual antiplatelet therapy (DAPT) or even a combination of both, i.e. triple therapy. Therefore, the purpose of this study, including such a high proportion of patients on antithrombotic therapy, was to investigate whether PDT in high-risk ICU patients is associated with elevated procedural complications and to analyse the risk factors for bleeding occurring during and after PDT.MethodsPDT interventions conducted in ICUs at 12 European sites between January 2016 and October 2019 were retrospectively analysed for procedural complications. For subgroup analyses, patient stratification into clinically relevant risk groups based on anticoagulation and antiplatelet treatment regimens was performed and the predictors of bleeding occurrence were analysed.ResultsIn total, 671 patients receiving PDT were included and stratified into four clinically relevant antithrombotic treatment groups: (1) intravenous unfractionated heparin (iUFH, prophylactic dosage) (n = 101); (2) iUFH (therapeutic dosage) (n = 131); (3) antiplatelet therapy (aspirin and/or P2Y12 receptor inhibitor) with iUFH (prophylactic or therapeutic dosage) except for triple therapy (n = 290) and (4) triple therapy (DAPT with iUFH in therapeutic dosage) (n = 149). Within the whole cohort, 74 (11%) bleedings were reported to be procedure-related. Bleeding occurrence during and after PDT was independently associated with low platelet count (OR 0.73, 95% CI [0.56, 0.92], p = 0.009), chronic kidney disease (OR 1.75, 95% CI [1.01, 3.03], p = 0.047) and previous stroke (OR 2.13, 95% CI [1.1, 3.97], p = 0.02).ConclusionIn this international, multicenter study bronchoscopy-guided PDT was a safe and low-complication airway management option, even in a cohort of high risk for bleeding on cardiovascular ICUs. Low platelet count, chronic kidney disease and previous stroke were identified as independent risk factors of bleeding during and after PDT but not triple therapy.

Percutaneous dilatational tracheotomy in high-risk ICU patients

Abstract Funding Acknowledgements Type of funding sources: None. Background Percutaneous dilatational tracheotomy (PDT) has become an established procedure in cardiac intensive care units (ICU). However, the safety of this method has been under debate given the growing number of critically ill patients with high bleeding risk receiving anticoagulation, dual antiplatelet therapy (DAPT) or even a combination of both, i.e. triple therapy. There is a need for critical evaluation of these safety concerns. This is the first and largest international, multicenter study on PDT to date including such a high proportion of patients on antithrombotic therapy investigating whether PDT in high-risk ICU patients is associated with elevated procedural complications and analysing risk factors for bleeding occurring during and after PDT. Methods PDT interventions conducted in ICUs at 12 European sites between January 2016 and October 2019 were retrospectively analysed for procedural complications. For subgroup analyses, patient stratification into clinically relevant risk groups based on anticoagulation and antiplatelet treatment regimens was performed. Procedure-related complications for each risk group were analysed until hospital discharge. Additionally, predictors of bleeding occurrence were analysed by uni- and multivariable regression models. Results In total, 671 patients receiving PDT according to Ciaglia’s technique with accompanying bronchoscopy were included. Patients were stratified into seven clinically relevant antithrombotic treatment groups. Within the whole cohort, 74 (11%) bleedings were reported to be procedure-related, none of which required surgical intervention. In almost all cases bleedings were associated with skin bleedings from the entry site and could easily be treated with minimally invasive stitching. Subgroup analysis showed no increase in the rate of procedure-related complications in patients with elevated body mass index. In a multivariable regression model bleeding occurrence during and after PDT was independently associated with platelet count (Odds ratio [OR] 0.73, 95% confidence interval [95% CI] [0.56, 0.92], p = 0.009), chronic kidney disease (OR 1.75, 95% CI [1.01, 3.03], p = 0.047) and previous stroke (OR 2.13, 95% CI [1.1, 3.97], p = 0.02). Neither PTT (OR 1.01, 95% CI [0.99, 1.02], p = 0.32), nor DAPT (OR 1.11, 95% CI [0.56, 2.04], p = 0.75) nor triple therapy (OR 0.93, 95% CI [0.49, 1.66], p = 0.82) were associated with bleeding risk. Conclusion In this international, multicenter study bronchoscopy-guided PDT was a safe and low-complication airway management option, even in a cohort of high risk for bleeding on cardiovascular ICUs. Platelet count, chronic kidney disease and previous stroke were identified as independent risk factors of bleeding during and after PDT whereas DAPT and triple therapy had no influence on bleeding events.

EARLY PALLIATIVE CARE INTERVENTION REDUCES ICU READMISSIONS IN HIGH-RISK PATIENTS

SESSION TITLE: Palliative Care and End-of-Life Issues Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: To determine whether a process of early palliative care intervention prompted by a patient-specific estimate of poor prognosis leads to improved patient outcomes in the medical intensive care unit (ICU). METHODS: We conducted a prospective two-phase study including usual care (UC) (N=53) and usual care plus targeted pro-active palliative care intervention (PC) (N=51) (either by consulting supportive care services or shared decision making discussion by the intensivists), each lasting four months on consecutive patients admitted to the ICU who survived ≥48 hours. For both phases, patients predicted to be at high risk (≥40% 6-month mortality) were identified using our validated integrated prognostic model1 [Surprise question “No” response-Would you be surprised if this patient died in the next six months?-, APACHE IV score, and Charlson Comorbidity Index (CCI) score]. RESULTS: Compared to UC, the pro-active PC intervention phase showed significant reduction in ICU readmissions (35.8% vs 16%, p=0.022) and increased identification of the patient’s legal decision maker (98% vs 83%, p=0.009). There were no differences in means between groups (UC vs PC) for age (67.9 vs 68.1 years, p=.938), CCI score (6.6 vs 6.1, p=.489), and mortality prediction model score (51.6 vs 54.3, p=.141). Intervention-arm patients had higher BMI (34.0 vs 28.3 kg/m2, p=0.005) and APACHE IV scores (65.3 vs 55.8, p=0.019), suggestive of a sicker critically ill patient population. There was no significant difference between groups (UC vs PC) in mean length of stay in ICU (5.5 vs 6.2 days, p=.454) or in hospital (13.0 vs 14.7 days, p=.466). There was no difference between groups (UC vs PC) in death at hospital discharge (60% vs 48%, p=.208). CONCLUSIONS: This pilot study demonstrates feasibility and improved patient-specific outcomes of end-of-life care. CLINICAL IMPLICATIONS: Systematic identification of high-risk ICU patients using the integrated mortality prediction model and pro-active primary palliative care intervention improves shared-decision making with the appropriate legal decision-maker and ICU readmission rates. This study promotes the role of family engagement and empowerment which is in compliance with Society of Critical Care Medicine (SCCM) ICU liberation bundle (A-F). These findings provide support for a large, multisite trial to see if they can be confirmed and if this approach represents a way to improve ICU patient care. DISCLOSURES: No relevant relationships by Lori Constantine, source=Web Response No relevant relationships by Stacey Culp, source=Web Response No relevant relationships by Sarah Hadique, source=Web Response No relevant relationships by Erica Mokaya, source=Web Response No relevant relationships by Alvin Moss, source=Web Response No relevant relationships by Hassan Mujahid, source=Web Response No relevant relationships by Rahul Sangani, source=Web Response

Meeting nutritional targets of critically ill patients by combined enteral and parenteral nutrition: review and rationale for the EFFORTcombo trial.

While medical nutrition therapy is an essential part of the care for critically ill patients, uncertainty exists about the right form, dosage, timing and route in relation to the phases of critical illness. As enteral nutrition (EN) is often withheld or interrupted during the intensive care unit (ICU) stay, combined EN and parenteral nutrition (PN) may represent an effective and safe option to achieve energy and protein goals as recommended by international guidelines. We hypothesise that critically ill patients at high nutritional risk may benefit from such a combined approach during their stay on the ICU. Therefore, we aim to test if an early combination of EN and high-protein PN (EN+PN) is effective in reaching energy and protein goals in patients at high nutritional risk, while avoiding overfeeding. This approach will be tested in the here-presented EFFORTcombo trial. Nutritionally high-risk ICU patients will be randomised to either high (≥2·2 g/kg per d) or low protein (≤1·2 g/kg per d). In the high protein group, the patients will receive EN+PN; in the low protein group, patients will be given EN alone. EN will be started in accordance with international guidelines in both groups. Efforts will be made to reach nutrition goals within 48-96 h. The efficacy of the proposed nutritional strategy will be tested as an innovative approach by functional outcomes at ICU and hospital discharge, as well as at a 6-month follow-up.

Lasting lessons learnt in the radiology department from the battle with COVID-19

Lasting lessons learnt in the radiology department from the battle with COVID-19

Cost-effectiveness of multi-layered silicone foam dressings for prevention of sacral and heel pressure ulcers in high-risk intensive care unit patients: An economic analysis of a randomised controlled trial.

Pressure ulcer incidence is high in intensive care units. This causes a serious financial burden to healthcare systems. We evaluated the cost‐effectiveness of multi‐layered silicone foam dressings for prevention of sacral and heel pressure ulcers in addition to standard prevention in high‐risk intensive care units patients. A randomised controlled trial to assess the efficacy of multi‐layered silicone foam dressings to prevent the development of pressure ulcers on heels and sacrum among 422 intensive care unit patients was conducted. Direct costs for preventive dressings in the intervention group and costs for treatment of incident pressure ulcers in both groups were measured using a bottom‐up approach. A cost‐effectiveness analysis by calculating the incremental cost‐effectiveness ratio using different assumptions was performed. Additional dressing and labour costs of €150.81 (€116.45 heels; €34.36 sacrum) per patient occurred in the intervention group. Treatment costs were €569.49 in the control group and €134.88 in the intervention group. The incremental cost‐effectiveness ratio was €1945.30 per PU avoided (€8144.72 on heels; €701.54 sacrum) in the intervention group. We conclude that application of preventive dressings is cost‐effective for the sacral area, but only marginal on heels for critically ill patients.

Chronic Critical Illness Patients Fail to Respond to Current Evidence-Based Intensive Care Nutrition Secondarily to Persistent Inflammation, Immunosuppression, and Catabolic Syndrome.

Sepsis-induced multiple-organ failure (MOF) has plagued surgical intensive care units (ICUs) for decades. Early nutrition (principally enteral) improves hospital outcomes of high-risk ICU patients. The purpose of this study is to document how the growing epidemic of chronic critical illness (CCI) patients responds to adequate evidence-based ICU nutrition. This retrospective post hoc subgroup analysis of an ongoing sepsis database identified 56 CCI patients who received early, adequate nutrition per an established surgical ICU protocol compared with 112 matched rapid-recovery (RAP) patients. The matched CCI and RAP groups had similar baseline characteristics. Serial biomarkers showed that CCI patients remained persistently inflamed with ongoing stress metabolism and that despite receiving evidence-based protocol nutrition, they had persistent catabolism and immunosuppression with more secondary infections. More CCI patients were discharged to poor nonhome destinations (ie, skilled nursing facilities, long-term acute care, hospice) (81% vs 29%, P < 0.05). At 12-month follow-up, CCI patients had worse functional status by Zubrod score (3.17 vs 1.62, P < 0.001) and Short Physical Battery Testing (4.78 vs 8.59, P < 0.02), worse health-related quality of life by EQ-5D-3L descriptive measures (9.07 vs 7.45, P < 0.003), and lower survival (67% vs 92%, P < 0.05). Despite early, adequate, evidence-based ICU nutrition, septic surgical ICU patients who develop CCI exhibit persistent inflammation, immunosuppression, and catabolism with unacceptable long-term morbidity and mortality. Although current evidence-based ICU nutrition may improve short-term ICU outcomes, novel adjuncts are needed to improve long-term outcomes for CCI patients.

The effectiveness of two silicone dressings for sacral and heel pressure ulcer prevention compared with no dressings in high-risk intensive care unit patients: a randomized controlled parallel-group trial.

There is a high incidence of pressure ulcers in high-risk settings such as intensive care. There is emerging evidence that the application of dressings to pressure ulcer predilection areas (sacrum and heels) improves prevention strategies. To determine whether preventive dressings, applied to the sacrum and heels of high-risk patients in intensive care units, in addition to standard prevention, reduces the incidence of pressure ulcers. Between June 2015 and July 2018, a randomized, controlled, two-arm, superiority pragmatic study was performed with a concealed 1:1 allocation to the intervention and control group. Patients assigned to the intervention group had dressings applied to the sacrum and heels. In total, 7575 patients were screened for eligibility and 475 patients were included and allocated to both groups. Finally, 212 patients in the intervention group and 210 in the control group were analysed. The mean age was 63·5 years and the majority of patients were male (65·4%). The cumulative pressure ulcer incidence category II and above was 2·8% in the intervention, and 10·5% in the control group (P = 0·001). Compared with the control group, the relative risk in the intervention group was 0·26 [95% confidence interval (CI) 0·11-0·62] and the absolute risk reduction was 0·08 (95% CI 0·03-0·13). The results indicate that the application of dressings, in addition to standard prevention, in high-risk intensive care unit patients is effective in preventing pressure ulcers at the heels and sacrum. What's already known about this topic? Pressure ulcers are severe soft tissue injuries and wounds, which occur worldwide in all healthcare settings. Despite preventive interventions, pressure ulcers still develop. There is emerging evidence that dressings help to prevent pressure ulcers. What does this study add? The incidence of pressure ulcers in intensive care units among high-risk patients remains high. The application of dressings to the sacrum and heels, in addition to standard preventive measures, reduces the relative and absolute risks for the development of pressure ulcers. The application of preventive dressings at the heels and sacrum seems to be feasible in intensive care settings.

The Challenge of Predicting Pressure Ulcers in Critically Ill Patients. A Multicenter Cohort Study.

Pressure ulcers are preventable events. Critically ill patients are particularly vulnerable. The Braden scale has been used to identify hospitalized patients at high risk for the development of pressure ulcers; however, this predictive tool has not been adequately validated for critically ill patients. We aimed to validate and improve the Braden scale for critically ill patients by adding clinical variables to the original scale. We conducted a cohort study in 12 intensive care units (ICUs) within a network of hospitals in Brazil during 2013. We excluded patients who stayed less than 48 hours, patients with one or more pressure ulcers at admission, and those who developed a pressure ulcer within the first 48 hours. We evaluated the Braden scale and clinical variables through a competing risk analysis. Discrimination and calibration were evaluated using the Concordance index (C-index) and a calibration plot, respectively. We used bootstrapping to assess internal validation. Our primary outcome was incident pressure ulcer within 30 days of ICU admission. We analyzed 9,605 patients and observed 157 pressure ulcers (rate of 3.33 pressure ulcers/1,000 patient-days). The majority of pressure ulcers were detected at stage I or II (28.7 and 66.2%, respectively). The Braden scale had good discrimination (C-index, 0.753; 95% confidence interval, 0.712-0.795), although its performance decreased for the most severely ill patients. We derived a modified predictive tool by adding eight clinical variables to the Braden scale: age, sex, diabetes mellitus, hematological malignancy, peripheral artery disease, hypotension at ICU admission, and need for mechanical ventilation or renal replacement therapy in the first 24 hours after ICU admission. The derived score had better discrimination and calibration than the original Braden scale. The best score cutoff was at least 6 points, with a sensitivity of 87% and a specificity of 71%. The original Braden scale measured at ICU admission is a valuable tool for pressure ulcer prediction, although it is not accurate for severely ill patients. To overcome the limitations of the original scale, we derived a modified score with better performance, which may identify high-risk ICU patients and support target interventions. External validation of the proposed clinical prediction score is needed.

Association of lectin pathway proteins with intra-abdominal Candida infection in high-risk surgical intensive-care unit patients. A prospective cohort study within the fungal infection network of Switzerland

Human studies on the role of mannose-binding lectin (MBL) in patients with invasive candidiasis have yielded conflicting results. We investigated the influence of MBL and other lectin pathway proteins on Candida colonization and intra-abdominal candidiasis (IAC) in a cohort of high-risk patients. Prospective observational cohort study of 89 high-risk intensive-care unit (ICU) patients. Levels of lectin pathway proteins at study entry and six MBL2 single-nucleotide polymorphisms were analyzed by sandwich-type immunoassays and genotyping, respectively, and correlated with development of heavy Candida colonization (corrected colonization index (CCI) ≥0.4) and occurrence of IAC during a 4-week period. Within 4 weeks after inclusion a CCI ≥0.4 and IAC was observed in 47% and 38% of patients respectively. Neither serum levels of MBL, ficolin-1, -2, -3, MASP-2 or collectin liver 1 nor MBL2 genotypes were associated with a CCI ≥0.4. Similarly, none of the analyzed proteins was found to be associated with IAC with the exception of lower MBL levels (HR 0.74, p = 0.02) at study entry. However, there was no association of MBL deficiency (<0.5 μg/ml), MBL2 haplo- or genotypes with IAC. Lectin pathway protein levels and MBL2 genotype investigated in this study were not associated with heavy Candida colonization or IAC in a cohort of high-risk ICU patients.

β-Glucan Antigenemia Anticipates Diagnosis of Blood Culture–Negative Intraabdominal Candidiasis

Life-threatening intraabdominal candidiasis (IAC) occurs in 30 to 40% of high-risk surgical intensive care unit (ICU) patients. Although early IAC diagnosis is crucial, blood cultures are negative, and the role of Candida score/colonization indexes is not established. The aim of this prospective Fungal Infection Network of Switzerland (FUNGINOS) cohort study was to assess accuracy of 1,3-β-d-glucan (BG) antigenemia for diagnosis of IAC. Four hundred thirty-four consecutive adults with abdominal surgery or acute pancreatitis and ICU stay 72 hours or longer were screened: 89 (20.5%) at high risk for IAC were studied (68 recurrent gastrointestinal tract perforation, 21 acute necrotizing pancreatitis). Diagnostic accuracy of serum BG (Fungitell), Candida score, and colonization indexes was compared. Fifty-eight of 89 (65%) patients were colonized by Candida; 29 of 89 (33%) presented IAC (27 of 29 with negative blood cultures). Nine hundred twenty-one sera were analyzed (9/patient): median BG was 253 pg/ml (46-9,557) in IAC versus 99 pg/ml (8-440) in colonization (P < 0.01). Sensitivity and specificity of two consecutive BG measurements greater than or equal to 80 pg/ml were 65 and 78%, respectively. In recurrent gastrointestinal tract perforation it was 75 and 77% versus 90 and 38% (Candida score ≥ 3), 79 and 34% (colonization index ≥ 0.5), and 54 and 63% (corrected colonization index ≥ 0.4), respectively. BG positivity anticipated IAC diagnosis (5 d) and antifungal therapy (6 d). Severe sepsis/septic shock and death occurred in 10 of 11 (91%) and 4 of 11 (36%) patients with BG 400 pg/ml or more versus 5 of 18 (28%, P = 0.002) and 1 of 18 (6%, P = 0.05) with BG measurement less than 400 pg/ml. β-Glucan decreased in IAC responding to therapy and increased in nonresponse. BG antigenemia is superior to Candida score and colonization indexes and anticipates diagnosis of blood culture-negative IAC. This proof-of-concept observation in strictly selected high-risk surgical ICU patients deserves investigation of BG-driven preemptive therapy.

Functional outcomes in high risk ICU patients in Central Australia: a prospective case series

This case series reports the functional outcomes of a prospective group of patients, thought to be at high risk for future morbidity, admitted to a rural intensive care unit (ICU) for a life-threatening illness. This prospective longitudinal observational study conducted between February and August 2009 in the Alice Springs Hospital ICU included patients considered 'high risk', as evidenced by profound physiological derangement. The participants were prospectively recruited when pre-defined criteria were met. Functional outcomes were measured by performance in the six-minute walk test, and the ability to undertake activities of daily living. Persisting morbidity was crudely measured by hospital re-admission rate. Mortality was measured at 6 months. Eighteen patients consented to take part in the study. Fourteen were Indigenous, and 14 were medical patients. Six-minute walk distance did not improve between ICU discharge and 6 months, and was significantly below that predicted. Almost all patients achieved scores consistent with full independence in basic activities of daily living. Five achieved scores consistent with independence in domestic activities of daily living. Twelve required at least one re-admission, with half the Indigenous subgroup requiring three or more re-admissions. There were four deaths, all Indigenous patients, and three were homeless.< This study demonstrates that follow up in this group at 6 months is both feasible and valuable. There is evidence of persisting morbidity, and increased mortality, particularly among Indigenous patients. Further avenues of research are suggested, including the need for a large multi-centre prospective study.

Psychological Symptoms of Family Members of High-Risk Intensive Care Unit Patients

Family members of patients in intensive care are at increased risk for psychological symptoms. To compare levels of posttraumatic stress disorder, anxiety, and depression during and 3 months after the intensive care experience in family members of patients at high risk for dying and to determine if differences were related to the patient's final disposition. Longitudinal descriptive study of 41 family members in 3 tertiary care intensive care units. By repeated-measures analysis of variance, family members' levels of posttraumatic stress disorder were significantly lower (P = .01) at 3 months after (mean score, 1.27; SD, 0.86) than during (mean, 1.61; SD, 0.81) the experience. Mean anxiety and depression scores were significantly lower (P < .001) after (anxiety: 7.35; SD, 3.91; depression: 5.63; SD, 4.58) than during (anxiety: 11.5; SD, 4.88; depression: 9.51; SD, 4.31) the experience. Scores for posttraumatic stress disorder, anxiety, and depression did not differ significantly between family members of patients who died and family members of patients who survived. Yet, all 13 family members of deceased patients and 42% of the total sample of 41 had traumatic stress scores of 1.5 or greater. Among the total sample, 44% had significant anxiety, and 27% were depressed. Family members' symptoms of posttraumatic stress disorder, anxiety, and depression significantly decreased 3 months after the intensive care experience and did not differ according to the patients' final disposition. However, many family members still had significant risk for posttraumatic stress disorder and borderline anxiety and depression at 3 months.

Pantoprazole for the Treatment of Peptic Ulcer Bleeding and Prevention of Rebleeding

Adding proton pump inhibitors (PPIs) to endoscopic therapy has become the mainstay of treatment for peptic ulcer bleeding, with current consensus guidelines recommending high-dose intravenous (IV) PPI therapy (IV bolus followed by continuous therapy). However, whether or not high-dose PPI therapy is more effective than low-dose PPI therapy is still debated. Furthermore, maintaining pH ≥ 4 appears to prevent mucosal bleeding in patients with acute stress ulcers; thus, stress ulcer prophylaxis with acid-suppressing therapy has been increasingly recommended in intensive care units (ICUs). This review evaluates the evidence for the efficacy of IV pantoprazole, a PPI, in preventing ulcer rebleeding after endoscopic hemostasis, and in controlling gastric pH and protecting against upper gastrointestinal (GI) bleeding in high-risk ICU patients. The review concludes that IV pantoprazole provides an effective option in the treatment of upper GI bleeding, the prevention of rebleeding, and for the prophylaxis of acute bleeding stress ulcers.

Symptoms experienced by intensive care unit patients at high risk of dying*

To provide a focused, detailed assessment of the symptom experiences of intensive care unit patients at high risk of dying and to evaluate the relationship between delirium and patients' symptom reports. Prospective, observational study of patients' symptoms. Two intensive care units in a tertiary medical center in the western United States. One hundred seventy-one intensive care unit patients at high risk of dying. None. Patients were interviewed every other day for up to 14 days. Patients rated the presence, intensity (1 = mild; 2 = moderate; 3 = severe), and distress (1 = not very distressing; 2 = moderately distressing; 3 = very distressing) of ten symptoms (that is, pain, tired, short of breath, restless, anxious, sad, hungry, scared, thirsty, confused). The Confusion Assessment Method-Intensive Care Unit was used to ascertain the presence of delirium. A total of 405 symptom assessments were completed by 171 patients. Patients' average age was 58 ± 15 yrs; 64% were males. Patients were mechanically ventilated during 34% of the 405 assessments, and 22% died in the hospital. Symptom prevalence ranged from 75% (tired) to 27% (confused). Thirst was moderately intense, and shortness of breath, scared, confusion, and pain were moderately distressful. Delirium was found in 34.2% of the 152 patients who could be evaluated. Delirious patients were more acutely ill and received significantly higher doses of opioids. Delirious patients were significantly more likely to report feeling confused (43% vs. 22%, p = .004) and sad (46% vs. 31%, p = .04) and less likely to report being tired (57% vs. 77%, p = .006) than nondelirious patients. Study findings suggest that unrelieved and distressing symptoms are present for the majority of intensive care unit patients, including those with delirium. Symptom assessment in high-risk intensive care unit patients may lead to more focused interventions to avoid or minimize unnecessary suffering.

Antifungal Prophylaxis and Pre-Emptive Therapy

In recent years, several reports have underlined the increasing role of fungal infections as a cause of morbidity and mortality in hospitalized non-haematological patients. For this reason, and also in light of the high mortality rate associated with these infections, chemoprophylaxis has been advocated for surgical patients hospitalized in intensive care units (ICUs). The available evidence suggests that the triazoles fluconazole and itraconazole are able to decrease Candida colonization and possibly infection compared with placebo, but this result has only been obtained in high-risk patients undergoing repeated surgical procedures for tertiary peritonitis. Consequently, triazole antifungal prophylaxis should be used with caution, and only in patients at high risk of invasive candidiasis, including high-risk surgical and ICU patients. A pre-emptive approach, defined as initiating antifungal treatment without confirmation of fungal infection, seems to be effective and safe.

Antifungal treatment strategies in high risk patients

We discuss different strategies for the treatment of invasive fungal infections (IFI) in high risk patients with a focus on patients experiencing profound and prolonged neutropenia, comprising those with acute myelogenous leukaemia (AML) or myelodysplastic syndrome (MDS) during remission induction chemotherapy and on patients undergoing allogeneic haematopoietic stem cell transplantation (SCT). Among these patients, invasive aspergillosis (IA) is the most frequently observed form of IFI, as opposed to high risk intensive care unit (ICU) patients in whom an increased incidence of invasive candidiasis (IC) can be observed. In both groups, initiation of early treatment has a profound impact on mortality rates, but adequate diagnostic tools are lacking. These circumstances have led to the parallel use of different treatment strategies, e.g. prophylaxis, empiric, pre-emptive and targeted treatment of IFI. The optimum treatment strategies for these severe infections are a matter of extensive research and discussion. A review of major clinical trials on the issue reveals that comparisons between different treatment strategies cannot be made. Considering the complexity of the issue, we advocate an eclectic treatment approach that reduces morbidity and mortality from IFI without compromising tolerability. In allogeneic HSCT recipients, patients receiving induction chemotherapy for AML or MDS and those under immunosuppressive medication for graft vs. host disease after allogeneic HSCT, we recommend prophylaxis with posaconazole. For empiric treatment of persistently febrile neutropenic patients, we opt for caspofungin as first and liposomal amphotericin B deoxycholate (L-AmB) as second line choice. If the diagnosis of IA can be established, voriconazole should be favoured over the alternative, liposomal amphotericin B (L-AmB). While high risk ICU patients benefit from fluconazole prophylaxis for IC, the choice of an optimal agent for targeted therapy depends largely on the neutrophil count. In non-neutropenic patients, we recommend an echinocandin as the first line treatment option. Patients with susceptible Candida spp. may be switched to fluconazole. Caspofungin or micafungin might be preferred to anidulafungin in the neutropenic patient. L-AmB is a valuable second line treatment option for both groups of patients.