Early or late parenteral nutrition: ASPEN vs. ESPEN

Citation

Casaer MP, Mesotten D, Hermans G et al. Early versus late parenteral nutrition in critically ill adults. N Engl J Med. 2011;365: 506-517.

Background

Controversy exists about the timing of the initiation of parenteral nutrition (PN) in critically ill adults in whom caloric targets cannot be met by enteral nutrition (EN) alone.

Methods

Objective

To compare early-initiation of PN (European guidelines) with late-initiation (American and Canadian guidelines) in adults who are receiving insufficient enteral nutrition in the intensive care unit (ICU).

Design

Prospective, randomized, controlled, parallel-group, multicenter clinical trial.

Setting

Seven multidisciplinary ICUs in Belgium.

Subjects

All adults admitted to participating ICUs with a nutritional risk score of 3 or more who did not meet any exclusion criteria.

Intervention

After enrollment, 2312 patients were randomized to receive PN 48 hours after ICU admission (early-initiation) and 2328 patients were randomized to receive PN on day 8 (late-initiation group). Both groups received early EN using a standardized protocol. PN was continued until EN met 80% of calorific goals, or when oral nutrition was resumed. It was restarted if enteral or oral feeding fell below 50% of calculated calorific needs.

Outcomes

Primary end point was the duration of dependency on intensive care, defined as the number of intensive care days and time to discharge from the ICU.

Results

The median stay in the ICU was one day shorter for the late-initiation group (3 v. 4; p = 0.02). The late-initiation group had a relative increase, of 6.3%, in the likelihood of being discharged earlier, and alive, from the ICU (hazard ratio 1.06; 95% confidence interval [CI] 1.00-1,13; p = 0.04). Rates of death in the ICU and survival at 90 days were similar between the two groups. The late-initiation group, as compared to the early-initiation group, had fewer ICU infections (22.8% v. 26.2%; p = 0.008), less days of renal replacement therapy (7 days (interquartile range [IQR] 3-16) v. 10 days (IQR 5-23); p = 0.008) and fewer patients requiring more than 2 days of mechanical ventilation (36.3% v. 40.2%; p = 0.006).

Conclusions

Late-initiation of PN was associated with faster recovery and fewer complications, when compared with early-initiation.

Trial Registration

{"type":"clinical-trial","attrs":{"text":"NCT00512122","term_id":"NCT00512122"}}NCT00512122     

Long-term outcome in early survivors of cardiogenic shock at the acute stage of myocardial infarction: a landmark analysis from the French registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction (FAST-MI) Registry

Introduction

There are little data about patients with cardiogenic shock (CS) who survive the early phase of acute myocardial infarction (AMI). The aim of this study was to assess long-term (5-year) mortality among early survivors of AMI, according to the presence of CS at the acute stage.

Methods

We analyzed 5-year follow-up data from the French registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction (FAST-MI) 2005 registry, a nationwide French survey including consecutive patients admitted for ST or non-ST-elevation AMI at the end of 2005 in 223 institutions.

Results

Of 3670 patients enrolled, shock occurred in 224 (6.1%), and 3411 survived beyond 30 days or hospital discharge, including 99 (2.9%) with shock. Early survivors with CS had a more severe clinical profile, more frequent concomitant in-hospital complications, and were less often managed invasively than those without CS.Five-year survival was 59% in patients with, versus 76% in those without shock (adjusted hazard ratio (HR) = 1.72 [1.24-2.38], P = 0.001). The excess of death associated with CS, however, was observed only during the first year (one-year survival: 77% vs 93%, adjusted HR: 2.87 [1.85 to 4.46] P <0.001), while survival from one to 5 years was similar (76% vs 82%, adjusted HR: 1.06 [0.64 to 1.74]). Propensity score-matched analyses yielded similar results.

Conclusions

In patients surviving the early phase of AMI, CS at the initial stage carries an increased risk of death up to one year after the acute event. Beyond one year, however, mortality is similar to that of patients without shock.

Trial registration

ClinicalTrials.gov number, {"type":"clinical-trial","attrs":{"text":"NCT00673036","term_id":"NCT00673036"}}NCT00673036, Registered May 5, 2008.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-014-0516-y) contains supplementary material, which is available to authorized users.     

Randomized trial comparing daily interruption of sedation and nursing-implemented sedation algorithm in medical intensive care unit patients

Introduction

Daily interruption of sedation (DIS) and sedation algorithms (SAs) have been shown to decrease mechanical ventilation (MV) duration. We conducted a randomized study comparing these strategies.

Methods

Mechanically ventilated adults 18 years old or older in the medical intensive care unit (ICU) were randomly assigned to DIS or SA. Exclusion criteria were severe neurocognitive dysfunction, administration of neuromuscular blockers, and tracheostomy. Study endpoints were total MV duration and 28-day ventilator-free survival.

Results

The study was terminated prematurely after 74 patients were enrolled (DIS 36 and SA 38). The two groups had similar age, gender, racial distribution, Acute Physiology and Chronic Health Evaluation II score, and reason for MV. The Data Safety Monitoring Board convened after DIS patients were found to have higher hospital mortality; however, no causal connection between DIS and increased mortality was identified. Interim analysis demonstrated a significant difference in primary endpoint, and study termination was recommended. The DIS group had longer total duration of MV (median 6.7 versus 3.9 days; P = 0.0003), slower improvement of Sequential Organ Failure Assessment over time (0.70 versus 0.23 units per day; P = 0.025), longer ICU length of stay (15 versus 8 days; P < 0.0001), and longer hospital length of stay (23 versus 12 days; P = 0.01).

Conclusion

In our cohort of patients, the use of SA was associated with reduced duration of MV and lengths of stay compared with DIS. Based on these results, DIS may not be appropriate in all mechanically ventilated patients.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00205517","term_id":"NCT00205517"}}NCT00205517.     

Are specialized ICUs so special?

Citation

Lott JP, Iwashyna TJ, Christie JD, Asch DA, Kramer AA, Kahn JM: Critical illness outcomes in specialty versus general intensive care units. Am J Respir Crit Care Med 2009, 179:676-683 [1].

Background

General intensive care units (ICUs) provide care across a wide range of diagnoses, whereas specialty ICUs provide diagnosis-specific care. Risk-adjusted outcome differences across such units are unknown.

Methods

Objective

To determine the association between specialty ICU care and the outcome of critical illness.

Design

Retrospective cohort study.

Setting

124 ICUs participating in the Acute Physiology and Chronic Health Evaluation IV from January 2002 to December 2005.

Subjects

84,182 patients admitted to specialty and general ICUs with an admitting diagnosis or procedure of acute coronary syndrome, ischemic stroke, intracranial hemorrhage, pneumonia, abdominal surgery, or coronaryartery bypass graft surgery. ICU type was determined by a local data coordinator at each site. Patients were classified by admission to a general ICU, a diagnosis-appropriate (ideal) specialty ICU, or a diagnosis-inappropriate (non-ideal) specialty ICU.

Intervention

None.

Outcomes

The primary outcomes were in-hospital mortality and ICU length of stay.

Results

After adjusting for important confounders, there were no significant differences in risk-adjusted mortality between general versus ideal specialty ICUs for all conditions other than pneumonia. Risk-adjusted mortality was significantly greater for patients admitted to non-ideal specialty ICUs. There was no consistent effect of specialization on length of stay for all patients or for ICU survivors.

Conclusion

Ideal specialty ICU care appears to offer no survival benefit over general ICU care for select common diagnoses. Non-ideal specialty ICU care (i.e., boarding) is associated with increased risk-adjusted mortality.     

Intensive insulin therapy in the medical ICU – not so sweet?

Citation

Van den Berghe G, Wilmer A, Hermans G, Meersseman W, Wouters PJ, Milants I, Van Wijngaerden E, Bobbaers H, Bouillon R: Intensive insulin therapy in the medical ICU. N.Engl.J.Med 2006; 354: 449-61 [1].

Background

Intensive insulin therapy reduces morbidity and mortality in patients in surgical intensive care units (ICUs), but its role in patients in medical ICUs is unknown.

Methods

Objective

To investigate the efficacy of intensive insulin therapy in medical ICU patients.

Design

Prospective, randomized, controlled trial

Setting

Medical ICU in Leuven, Belgium.

Subjects

1200 medical ICU patients anticipated to need intensive care for at least three days.

Intervention

On admission, patients were randomly assigned to strict normalization of blood glucose levels (80 to 110 mg per deciliter [4.4 to 6.1 mmol per liter]) with the use of insulin infusion or to conventional therapy (insulin administered when the blood glucose level exceeded 215 mg per deciliter [12 mmol per liter], with the infusion tapered when the level fell below 180 mg per deciliter [10 mmol per liter]).

Measurements and main results

There was a history of diabetes in 16.9 percent of the patients. In the intention-to-treat analysis of 1200 patients, intensive insulin therapy reduced blood glucose levels but did not significantly reduce in-hospital mortality (40.0 percent in the conventional-treatment group vs. 37.3 percent in the intensive-treatment group, P = 0.33). However, morbidity was significantly reduced by the prevention of newly acquired kidney injury, accelerated weaning from mechanical ventilation, and accelerated discharge from the ICU and the hospital. Although length of stay in the ICU could not be predicted on admission, among 433 patients who stayed in the ICU for less than three days, mortality was greater among those receiving intensive insulin therapy. In contrast, among 767 patients who stayed in the ICU for three or more days, inhospital mortality in the 386 who received intensive insulin therapy was reduced from 52.5 to 43.0 percent (P = 0.009) and morbidity was also reduced.

Conclusion

Intensive insulin therapy significantly reduced morbidity but not mortality among all patients in the medical ICU. Although the risk of subsequent death and disease was reduced in patients treated for three or more days, these patients could not be identified before therapy. Further studies are needed to confirm these preliminary data. (ClinicalTrials.gov number, {"type":"clinical-trial","attrs":{"text":"NCT00115479","term_id":"NCT00115479"}}NCT00115479).     

Clinical outcomes of patients requiring ventilatory support in Brazilian intensive care units: a multicenter,prospective, cohort study

Introduction

Contemporary information on mechanical ventilation (MV) use in emerging countries is limited. Moreover, most epidemiological studies on ventilatory support were carried out before significant developments, such as lung protective ventilation or broader application of non-invasive ventilation (NIV). We aimed to evaluate the clinical characteristics, outcomes and risk factors for hospital mortality and failure of NIV in patients requiring ventilatory support in Brazilian intensive care units (ICU).

Methods

In a multicenter, prospective, cohort study, a total of 773 adult patients admitted to 45 ICUs over a two-month period requiring invasive ventilation or NIV for more than 24 hours were evaluated. Causes of ventilatory support, prior chronic health status and physiological data were assessed. Multivariate analysis was used to identifiy variables associated with hospital mortality and NIV failure.

Results

Invasive MV and NIV were used as initial ventilatory support in 622 (80%) and 151 (20%) patients. Failure with subsequent intubation occurred in 54% of NIV patients. The main reasons for ventilatory support were pneumonia (27%), neurologic disorders (19%) and non-pulmonary sepsis (12%). ICU and hospital mortality rates were 34% and 42%. Using the Berlin definition, acute respiratory distress syndrome (ARDS) was diagnosed in 31% of the patients with a hospital mortality of 52%. In the multivariate analysis, age (odds ratio (OR), 1.03; 95% confidence interval (CI), 1.01 to 1.03), comorbidities (OR, 2.30; 95% CI, 1.28 to 3.17), associated organ failures (OR, 1.12; 95% CI, 1.05 to 1.20), moderate (OR, 1.92; 95% CI, 1.10 to 3.35) to severe ARDS (OR, 2.12; 95% CI, 1.01 to 4.41), cumulative fluid balance over the first 72 h of ICU (OR, 2.44; 95% CI, 1.39 to 4.28), higher lactate (OR, 1.78; 95% CI, 1.27 to 2.50), invasive MV (OR, 2.67; 95% CI, 1.32 to 5.39) and NIV failure (OR, 3.95; 95% CI, 1.74 to 8.99) were independently associated with hospital mortality. The predictors of NIV failure were the severity of associated organ dysfunctions (OR, 1.20; 95% CI, 1.05 to 1.34), ARDS (OR, 2.31; 95% CI, 1.10 to 4.82) and positive fluid balance (OR, 2.09; 95% CI, 1.02 to 4.30).

Conclusions

Current mortality of ventilated patients in Brazil is elevated. Implementation of judicious fluid therapy and a watchful use and monitoring of NIV patients are potential targets to improve outcomes in this setting.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01268410","term_id":"NCT01268410"}}NCT01268410.     

Calorie intake and patient outcomes in severe acute kidney injury: findings from The Randomized Evaluation of Normal vs. Augmented Level of Replacement Therapy (RENAL) study trial

Introduction

Current practice in the delivery of caloric intake (DCI) in patients with severe acute kidney injury (AKI) receiving renal replacement therapy (RRT) is unknown. We aimed to describe calorie administration in patients enrolled in the Randomized Evaluation of Normal vs. Augmented Level of Replacement Therapy (RENAL) study and to assess the association between DCI and clinical outcomes.

Methods

We performed a secondary analysis in 1456 patients from the RENAL trial. We measured the dose and evolution of DCI during treatment and analyzed its association with major clinical outcomes using multivariable logistic regression, Cox proportional hazards models, and time adjusted models.

Results

Overall, mean DCI during treatment in ICU was low at only 10.9 ± 9 Kcal/kg/day for non-survivors and 11 ± 9 Kcal/kg/day for survivors. Among patients with a lower DCI (below the median) 334 of 729 (45.8%) had died at 90-days after randomization compared with 316 of 727 (43.3%) patients with a higher DCI (above the median) (P = 0.34). On multivariable logistic regression analysis, mean DCI carried an odds ratio of 0.95 (95% confidence interval (CI): 0.91-1.00; P = 0.06) per 100 Kcal increase for 90-day mortality. DCI was not associated with significant differences in renal replacement (RRT) free days, mechanical ventilation free days, ICU free days and hospital free days. These findings remained essentially unaltered after time adjusted analysis and Cox proportional hazards modeling.

Conclusions

In the RENAL study, mean DCI was low. Within the limits of such low caloric intake, greater DCI was not associated with improved clinical outcomes.

Trial registration

ClinicalTrials.gov number, {"type":"clinical-trial","attrs":{"text":"NCT00221013","term_id":"NCT00221013"}}NCT00221013     

Association of body temperature and antipyretic treatments with mortality of critically ill patients with and without sepsis: multi-centered prospective observational study

Introduction

Fever is frequently observed in critically ill patients. An independent association of fever with increased mortality has been observed in non-neurological critically ill patients with mixed febrile etiology. The association of fever and antipyretics with mortality, however, may be different between infective and non-infective illness.

Methods

We designed a prospective observational study to investigate the independent association of fever and the use of antipyretic treatments with mortality in critically ill patients with and without sepsis. We included 1,425 consecutive adult critically ill patients (without neurological injury) requiring > 48 hours intensive care admitted in 25 ICUs. We recorded four-hourly body temperature and all antipyretic treatments until ICU discharge or 28 days after ICU admission, whichever occurred first. For septic and non-septic patients, we separately assessed the association of maximum body temperature during ICU stay (MAX_ICU) and the use of antipyretic treatments with 28-day mortality.

Results

We recorded body temperature 63,441 times. Antipyretic treatment was given 4,863 times to 737 patients (51.7%). We found that treatment with non-steroidal anti-inflammatory drugs (NSAIDs) or acetaminophen independently increased 28-day mortality for septic patients (adjusted odds ratio: NSAIDs: 2.61, P = 0.028, acetaminophen: 2.05, P = 0.01), but not for non-septic patients (adjusted odds ratio: NSAIDs: 0.22, P = 0.15, acetaminophen: 0.58, P = 0.63). Application of physical cooling did not associate with mortality in either group. Relative to the reference range (MAX_ICU 36.5°C to 37.4°C), MAX_ICU ≥ 39.5°C increased risk of 28-day mortality in septic patients (adjusted odds ratio 8.14, P = 0.01), but not in non-septic patients (adjusted odds ratio 0.47, P = 0.11).

Conclusions

In non-septic patients, high fever (≥ 39.5°C) independently associated with mortality, without association of administration of NSAIDs or acetaminophen with mortality. In contrast, in septic patients, administration of NSAIDs or acetaminophen independently associated with 28-day mortality, without association of fever with mortality. These findings suggest that fever and antipyretics may have different biological or clinical or both implications for patients with and without sepsis.

Trial registration

ClinicalTrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT00940654","term_id":"NCT00940654"}}NCT00940654     

Early fluid resuscitation with hydroxyethyl starch 130/0.4 (6%) in severe burn injury: a randomized,controlled, double-blind clinical trial

Introduction

There are limited data on the efficacy of early fluid resuscitation with third-generation hydroxyethyl starch (HES 130) in burn injury. Adverse effects of HES on survival and organ function have been reported.

Methods

In this randomized, controlled, double-blind trial, 48 patients with severe burn injury were assigned to receive either lactated Ringer’s solution plus 6% HES 130/0.4 in a ratio of 2:1 or lactated Ringer’s solution with no colloid supplement for the first 72 hours. Primary outcome parameter was the group difference of administered total fluid from intensive care unit (ICU) admission up to day 3. Secondary outcomes included kidney and lung injury and failure, length of stay, and mortality.

Results

Three-day totals of administered resuscitation fluid (medians) were 21,190 mL in the lactated Ringer’s group and 19,535 mL in the HES group (HES: −1,213 mL; P = 0.39). Creatinine levels from day 1 to 3 (HES: +0.4 μmol/L; 95% confidence interval (CI) −18.7 to 19.5; P = 0.97) and urinary outputs from day 1 to 3 (HES: −58 mL; 95% CI −400 to 283; P = 0.90) were not different. Six patients in each group developed acute respiratory distress syndrome (ARDS) (risk ratio 0.96; 95% CI 0.35 to 2.64; P = 0.95). Length of ICU stay (HES vs. lactated Ringer’s: 28 vs. 24 days; P = 0.80) and length of hospital stay (31 vs. 29 days; P = 0.57) were similar. Twenty-eight-day mortality was 4 patients in each group (risk ratio 0.96; 95% CI 0.27 to 4.45; P = 0.95), and in-hospital mortality was 8 in the HES group vs. 5 patients in the lactated Ringer’s group (hazard ratio 1.86; 95% CI 0.56 to 6.19; P = 0.31).

Conclusions

There was no evidence that early fluid resuscitation with balanced HES 130/0.4 (6%) in addition to lactated Ringer’s solution would lead to a volume-sparing effect in severe burn injury. Together with the findings that early renal function, incidence of ARDS, length of stay, and mortality were not negatively influenced by HES in this setting, balanced HES 130/0.4 (6%) plus lactated Ringer’s solution could not be considered superior to lactated Ringer’s solution alone.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01012648","term_id":"NCT01012648"}}NCT01012648     

Impact of four sequential measures on the prevention of ventilator-associated pneumonia in cardiac surgery patients

Introduction

Ventilator-associated pneumonia (VAP) is the most frequent infection in patients admitted to intensive care units.The efficacy of individual measures for the prevention of VAP is well documented, and data on the impact of implementing bundle measures have usually been reported from studies in which several measures are implemented simultaneously in the general intensive care unit (ICU).The objective of our work was to evaluate the impact of four sequentially implemented measures for preventing VAP in a major heart surgery ICU. The measures were a specific training program, aspiration of subglottic secretions (ASSs), introduction of an inclinometer to improve the semirecumbent position, and reinforcement of oral care with chlorhexidine.

Methods

We compared rates of VAP, days on mechanical ventilation (MV), and cost of antimicrobial agents before and during implementation.

Results

We collected data from 401 patients before the intervention and from 1,534 patients during the intervention. Both groups were comparable. No significant differences in EuroSCORE were observed between the patients of both periods (6.4 versus 6.3; P = 0.7). The rates of VAP (episodes/1,000 days of ventilation) were, respectively, 23.9 versus 13.5 (P = 0.005). Mean number of days of MV/1,000 days of stay was 507 versus 375 (P = 0.001), and the cost of antimicrobial therapy (Euros/1,000 days of stay) was €70,612 versus €52,775 (P = 0.10). The main effect of sequential application of preventive measures in time achieved a relative-rate reduction of VAP of 41% (IRR, 0.41; 95% CI, 0.28 to 0.62). The mortality rate before and during the intervention was 13.0% and 10.2%, respectively.VAP rate was most significantly reduced by training and the use of the inclinometer.

Conclusions

A sequentially applied bundle of four preventive measures reduces VAP rates, days of MV, and the cost of antimicrobial therapy in patients admitted to the major heart surgery ICU.

Trial registration

Clinical Trials.gov: {"type":"clinical-trial","attrs":{"text":"NCT02060045","term_id":"NCT02060045"}}NCT02060045. Registered 4 February 2014.     

Cardiac arrest patients have an impaired immune response,which is not influenced by induced hypothermia

Introduction

Induced hypothermia is increasingly applied as a therapeutic intervention in ICUs. One of the underlying mechanisms of the beneficial effects of hypothermia is proposed to be reduction of the inflammatory response. However, a fear of reducing the inflammatory response is an increased infection risk. Therefore, we studied the effect of induced hypothermia on immune response after cardiac arrest.

Methods

A prospective observational cohort study in a mixed surgical-medical ICU. Patients admitted at the ICU after surviving cardiac arrest were included and during 24 hours body temperature was strictly regulated at 33°C or 36°C. Blood was drawn at three time points: after reaching target temperature, at the end of the target temperature protocol and after rewarming to 37°C. Plasma cytokine levels and response of blood leucocytes to stimulation with toll-like receptor (TLR) ligands lipopolysaccharide (LPS) from Gram-negative bacteria and lipoteicoic acid (LTA) from Gram-positive bacteria were measured. Also, monocyte HLA-DR expression was determined.

Results

In total, 20 patients were enrolled in the study. Compared to healthy controls, cardiac arrest patients kept at 36°C (n = 9) had increased plasma cytokines levels, which was not apparent in patients kept at 33°C (n = 11). Immune response to TLR ligands in patients after cardiac arrest was generally reduced and associated with lower HLA-DR expression. Patients kept at 33°C had preserved ability of immune cells to respond to LPS and LTA compared to patients kept at 36°C. These differences disappeared over time. HLA-DR expression did not differ between 33°C and 36°C.

Conclusions

Patients after cardiac arrest have a modest systemic inflammatory response compared to healthy controls, associated with lower HLA-DR expression and attenuated immune response to Gram-negative and Gram-positive antigens, the latter indicative of an impaired immune response to bacteria. Patients with a body temperature of 33°C did not differ from patients with a body temperature of 36°C, suggesting induced hypothermia does not affect immune response in patients with cardiac arrest.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01020916","term_id":"NCT01020916"}}NCT01020916, registered 25 November 2009     

The effects of discharge to an intermediate care unit after a critical illness: A 5-year cohort study

Purpose

The impact of the intermediate care unit (IMCU) on post–intensive care unit (ICU) outcomes is controversial.

Materials and Methods

We analyzed admissions from January 2003 to December 2008 from a mixed ICU in a teaching hospital in Brazil with a high patient-to-nurse ratio (3.5:1 on the ICU, 11:1 on the IMCU, 20-25:1 on the ward). A retrospective propensity-matched analysis was performed with data from 690 patients who were discharged after at least 3 days of ICU stay.

Results

Of the 690 patients, 160 (23%) were discharged to the IMCU. A total of 399 propensity-matched patients were compared: 298 were discharged to the ward and 101 were discharged to the IMCU. Ninety-day mortality rate was similar between the IMCU and ward patients (22% vs 18%, respectively, P = .37), as was the unplanned ICU readmission rate (P = .63). In a multivariate logistic regression, discharge to the IMCU had no effect on the 90-day mortality rate (P = .27).

Conclusions

In a resource-limited setting with a high patient-to-nurse ratio, discharge to IMCU had no impact on 90-day mortality rate and on unplanned readmission rate. The impact of discharge to the IMCU on the outcome for critically ill patients should be evaluated in further studies.     

Methods for a study of Anticipatory and Preventive multidisciplinary Team Care in a family practice

BACKGROUND

T o examine the methodology used to evaluate whether focusing the work of nurse practitioners and a pharmacist on frail and at-risk patients would improve the quality of care for such patients.

DESIGN

Evaluation of methodology of a randomized controlled trial including analysis of quantitative and qualitative data over time and analysis of cost-effectiveness.

SETTING

A single practice in a rural area near Ottawa, Ont.

PARTICIPANTS

A total of 241 frail patients, aged 50 years and older, at risk of experiencing adverse health outcomes.

INTERVENTION

At-risk patients were randomly assigned to receive Anticipatory and Preventive Team Care (from their family physicians, 1 of 3 nurse practitioners, and a pharmacist) or usual care.

MAIN OUTCOME MEASURES

The principal outcome for the study was the quality of care for chronic disease management. Secondary outcomes included other quality of care measures and evaluation of the program process and its cost-effectiveness. This article examines the effectiveness of the methodology used. Quantitative data from surveys, administrative databases, and medical records were supplemented with qualitative information from interviews, focus groups, work logs, and study notes.

CONCLUSION

Three factors limit our ability to fully demonstrate the potential effects of this team structure. For reasons outside our control, the intervention duration was shorter than intended; the practice’s physical layout did not facilitate interactions between the care providers; and contamination of the intervention effect into the control arm cannot be excluded. The study used a randomized design, relied on a multifaceted approach to evaluating its effects, and used several sources of data.

TRIAL REGISTRATION NUMBER

{"type":"clinical-trial","attrs":{"text":"NCT00238836","term_id":"NCT00238836"}}NCT00238836 (CONSORT).     

Nighttime intensivist staffing and the timing of death among ICU decedents: a retrospective cohort study

Introduction

Intensive care units (ICUs) are increasingly adopting 24-hour intensivist physician staffing. Although nighttime intensivist staffing does not consistently reduce mortality, it may affect other outcomes such as the quality of end-of-life care.

Methods

We conducted a retrospective cohort study of ICU decedents using the 2009–2010 Acute Physiology and Chronic Health Evaluation clinical information system linked to a survey of ICU staffing practices. We restricted the analysis to ICUs with high-intensity daytime staffing, in which the addition of nighttime staffing does not influence mortality. We used multivariable regression to assess the relationship between nighttime intensivist staffing and two separate outcomes potentially related to the quality of end-of-life care: time from ICU admission to death and death at night.

Results

Of 30,456 patients admitted to 27 high-intensity daytime staffed ICUs, 3,553 died in the hospital within 30 days. After adjustment for potential confounders, admission to an ICU with nighttime intensivist staffing was associated with a shorter duration between ICU admission and death (adjusted difference: –2.5 days, 95% CI -3.5 to -1.5, p-value < 0.001) and a decreased odds of nighttime death (adjusted odds ratio: 0.75, 95% CI 0.60 to 0.94, p-value 0.011) compared to admission to an ICU without nighttime intensivist staffing.

Conclusions

Among ICU decedents, nighttime intensivist staffing is associated with reduced time between ICU admission and death and reduced odds of nighttime death.     

Intensivists: don't quit your day job...yet!

Citation

Levy MM, Rapoport J, Lemeshow S, Chalfin DB, Phillips G, and Danis M: Association between Critical Care Physician Management and Patient Mortality in the Intensive Care Unit. Ann Intern Med 2008 Jun 3, 148(11): 801-9 [1].

Background

Critically ill patients admitted to intensive care units (ICUs) are thought to gain an added survival benefit from management by critical care physicians, but evidence of this benefit is scant.

Methods

Objective

To examine the association between hospital mortality in critically ill patients and management by critical care physicians.

Design

Retrospective analysis of a large, prospectively collected database of critically ill patients.

Setting

123 ICUs in 100 U.S. hospitals.

Subjects

101,832 critically ill adults.

Intervention

None.

Outcomes

Through use of a random-effects logistic regression, investigators compared hospital mortality between patients cared for entirely by critical care physicians and patients cared for entirely by non-critical care physicians. An expanded Simplified Acute Physiology Score was used to adjust for severity of illness, and a propensity score was used to adjust for differences in the probability of selective referral of patients to critical care physicians.

Results

Patients who received critical care management (CCM) were generally sicker, received more procedures, and had higher hospital mortality rates than those who did not receive CCM. After adjustment for severity of illness and propensity score, hospital mortality rates were higher for patients who received CCM than for those who did not. The difference in adjusted hospital mortality rates was less for patients who were sicker and who were predicted by propensity score to receive CCM. Residual confounders for illness severity and selection biases for CCM might exist that were inadequately assessed or recognized.

Conclusion

In a large sample of ICU patients in the United States, the odds of hospital mortality were higher for patients managed by critical care physicians than those who were not. Additional studies are needed to further evaluate these results and clarify the mechanisms by which they might occur.     

Insulin treatment guided by subcutaneous continuous glucose monitoring compared to frequent point-of-care measurement in critically ill patients: a randomized controlled trial

Introduction

Glucose measurement in intensive care medicine is performed intermittently with the risk of undetected hypoglycemia. The workload for the ICU nursing staff is substantial. Subcutaneous continuous glucose monitoring (CGM) systems are available and may be able to solve some of these issues in critically ill patients.

Methods

In a randomized controlled design in a mixed ICU in a teaching hospital we compared the use of subcutaneous CGM with frequent point of care (POC) to guide insulin treatment. Adult critically ill patients with an expected stay of more than 24 hours and in need of insulin therapy were included. All patients received subcutaneous CGM. CGM data were blinded in the control group, whereas in the intervention group these data were used to feed a computerized glucose regulation algorithm. The same algorithm was used in the control group fed by intermittent POC glucose measurements. Safety was assessed with the incidence of severe hypoglycemia (<2.2 mmol/L), efficacy with the percentage time in target range (5.0 to 9.0 mmol/L). In addition, we assessed nursing workload and costs.

Results

In this study, 87 patients were randomized to the intervention and 90 to the control group. CGM device failure resulted in 78 and 78 patients for analysis. The incidence of severe glycemia and percentage of time within target range was similar in both groups. A significant reduction in daily nursing workload for glucose control was found in the intervention group (17 versus 36 minutes; P <0.001). Mean daily costs per patient were significantly reduced with EUR 12 (95% CI −32 to −18, P = 0.02) in the intervention group.

Conclusions

Subcutaneous CGM to guide insulin treatment in critically ill patients is as safe and effective as intermittent point-of-care measurements and reduces nursing workload and daily costs. A new algorithm designed for frequent measurements may lead to improved performance and should precede clinical implementation.

Trial registration

Clinicaltrials.gov, {"type":"clinical-trial","attrs":{"text":"NCT01526044","term_id":"NCT01526044"}}NCT01526044. Registered 1 February 2012.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-014-0453-9) contains supplementary material, which is available to authorized users.     

Interactions between the volume effects of hydroxyethyl starch 130/0.4 and Ringer′s acetate

Introduction

The turnover of Ringer´s solutions is greatly dependent on the physiological situation, such as the presence of dehydration or anaesthesia. The present study evaluates whether the kinetics is affected by previous infusion of colloid fluid.

Methods

Ten male volunteers with a mean age of 22 years underwent three infusion experiments, on separate days and in random order. The experiments included 10 mL/kg of 6% hydroxyethyl starch 130/0.4 (Voluven™), 20 mL/kg of Ringer''s acetate, and a combination of both, where Ringer´s was administered 75 minutes after the starch infusion ended. The kinetics of the volume expansion was analysed by non-linear least- squares regression, based on urinary excretion and serial measurement of blood haemoglobin concentration for up to 420 minutes.

Results

The mean volume of distribution of the starch was 3.12 L which agreed well with the plasma volume (3.14 L) estimated by anthropometry. The volume expansion following the infusion of starch showed monoexponential elimination kinetics with a half-life of two hours. Two interaction effects were found when Ringer´s acetate was infused after the starch. First, there was a higher tendency for Ringer´s acetate to distribute to a peripheral compartment at the expense of the plasma volume expansion. The translocated amount of Ringer´s was 70% higher when HES had been infused earlier. Second, the elimination half-life of Ringer´s acetate was five times longer when administered after the starch (88 versus 497 minutes, P <0.02).

Conclusions

Starch promoted peripheral accumulation of the later infused Ringer´s acetate solution and markedly prolonged the elimination half-life.

Trial registration

ClinicalTrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT01195025","term_id":"NCT01195025"}}NCT01195025     

Argatroban versus Lepirudin in critically ill patients (ALicia): a randomized controlled trial

Introduction

Critically ill patients often require renal replacement therapy accompanied by thrombocytopenia. Thrombocytopenia during heparin anticoagulation may be due to heparin-induced thrombocytopenia with need for alternative anticoagulation. Therefore, we compared argatroban and lepirudin in critically ill surgical patients.

Methods

Following institutional review board approval and written informed consent, critically ill surgical patients more than or equal to 18 years with suspected heparin-induced thrombocytopenia, were randomly assigned to receive double-blind argatroban or lepirudin anticoagulation targeting an activated Partial Thromboplastin Time (aPTT) of 1.5 to 2 times baseline. In patients requiring continuous renal replacement therapy we compared the life-time of hemodialysis filters. We evaluated in all patients the incidence of bleeding and thrombembolic events.

Results

We identified 66 patients with suspected heparin-induced thrombocytopenia, including 28 requiring renal replacement therapy. Mean filter lifetimes did not differ between groups (argatroban 32 ± 25 hours (n = 12) versus lepirudin 27 ± 21 hours (n = 16), mean difference 5 hours, 95% CI −13 to 23, P = 0.227). Among all 66 patients, relevant bleeding occurred in four argatroban- versus eleven lepirudin-patients (OR 3.9, 95% CI 1.1 to 14.0, P = 0.040). In the argatroban-group, three thromboembolic events occurred compared to two in the lepirudin group (OR 0.7, 95% CI 0.1 to 4.4, P = 0.639). The incidence of confirmed heparin-induced thrombocytopenia was 23% (n = 15) in our study population.

Conclusions

This first randomized controlled double-blind trial comparing two direct thrombin inhibitors showed comparable effectiveness for renal replacement therapy, but suggests fewer bleeds in surgical patients with argatroban anticoagulation.

Trial registration

Clinical Trials.gov {"type":"clinical-trial","attrs":{"text":"NCT00798525","term_id":"NCT00798525"}}NCT00798525. Registered 25 November 2008

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-014-0588-8) contains supplementary material, which is available to authorized users.     

Effect of Intraoperative Paracetamol on Catheter-Related Bladder Discomfort: A Prospective,Randomized, Double-Blind Study

Background

The insertion of urinary catheters during urinary surgical interventions may lead to catheter-related bladder discomfort (CRBD) in the postoperative period.

Objective

We aimed to evaluate the effect of single-dose intravenous paracetamol on CRBD.

Methods

In this randomized, controlled, double-blind study, 64 patients (age >18 years, American Society of Anesthesiologists Physical Status I–II) requiring urinary bladder catheterization for percutaneous nephrolithotomy were assigned to groups that received either intravenous paracetamol (15 mg/kg) (group P) or NaCl 0.9% solution (control group [group C]) 30 minutes before the end of surgery. Patients received patient-controlled analgesia (10-mg bolus of meperidine, without infusion, 20-minute lock out) postoperatively. CRBD and pain status were assessed at 30 minutes and 1, 2, 4, 6, and 12 hours postoperatively. Postoperative meperidine requirement and patient and surgeon satisfaction were assessed.

Results

Group P had significantly lower CRBD scores at all time points except at 12 hours postoperatively compared with group C (P < 0.05). Total meperidine consumption was significantly higher in group C (P < 0.05). Patient and surgeon satisfaction scores were significantly higher in group P (P < 0.05).

Conclusions

Intraoperative single-dose paracetamol was found to be effective in reducing the severity of CRBD and pain in urologic surgery. We suggest that it may be an efficient, reliable, easy-to-apply drug for CRBD. ClinicalTrials.gov identifier: NCT01652183.Key words: catheter-related bladder discomfort, intravenous paracetamol, urologic surgery     

Visitation policies and practices in US ICUs

Introduction

Prior reports suggest that restrictive ICU visitation policies can negatively impact patients and their loved ones. However, visitation practices in US ICUs, and the hospital factors associated with them, are not well described.

Methods

A telephone survey was made of ICUs, stratified by US region and hospital type (community, federal, or university), between 2008 and 2009. Hospital characteristics were self-reported and included the hospitals'' bed number, critical care unit number, and presence of ICU leadership. Hospital and ICU visitation restrictions were based on five criteria: visiting hours; visit duration; number of visitors; age of visitors; and membership in the patient''s immediate family. Hospitals or ICUs without restrictions had open visitation policies; those with any restriction had restrictive policies.

Results

The study surveyed 606 hospitals in the Northeast (17.0%), Midwest (26.2%), South (36.6%), and West (20.1%) regions; most were community hospitals (n = 401, 66.2%). The mean hospital size was 239 ± 217 beds; the mean percentage of ICU beds was 11.6% ± 13.4%. Hospitals often had restrictive hospital (n = 463, 76.4%) and ICU (n = 543, 89.6%) visitation policies. Many ICUs had ≥ 3 restrictions (n = 375; 61.9%), most commonly related to visiting hours and visitor number or age. Nearly all ICUs allowed visitation exceptions (n = 474; 94.8%). ICUs with open policies were more common in hospitals with < 150 beds. Among restrictive ICUs, the bed size, hospital type, number of critical care units, and ICU leadership were not associated with the number of restrictions. On average, hospitals in the Midwest had the least restrictive policies, while those in the Northeast had the most restrictive.

Conclusion

In 2008 the overwhelming majority of US ICUs in this study had restrictive visitation policies. Wide variability in visitation policies suggests that further study into the impact of ICU visitations on care and outcomes remains necessary to standardize practice.