The Impact of Nursing Delirium Preventive Interventions in the ICU: A Multicenter Cluster-randomized Controlled Clinical Trial.

Rationale: Delirium is common in critically ill patients and is associated with deleterious outcomes. Nonpharmacological interventions are recommended in current delirium guidelines, but their effects have not been unequivocally established. Objectives: To determine the effects of a multicomponent nursing intervention program on delirium in the ICU. Methods: A stepped-wedge cluster-randomized controlled trial was conducted in ICUs of 10 centers. Adult critically ill surgical, medical, or trauma patients at high risk of developing delirium were included. A multicomponent nursing intervention program focusing on modifiable risk factors was implemented as standard of care. The primary outcome was the number of delirium-free and coma-free days alive in 28 days after ICU admission. Measurements and Main Results: A total of 1,749 patients were included. Time spent on interventions per 8-hour shift was median (interquartile range) 38 (14-116) minutes in the intervention period and median 32 (13-73) minutes in the control period (P = 0.44). Patients in the intervention period had a median of 23 (4-27) delirium-free and coma-free days alive compared with a median of 23 (5-27) days for patients in the control group (mean difference, -1.21 days; 95% confidence interval, -2.84 to 0.42 d; P = 0.15). In addition, the number of delirium days was similar: median 2 (1-4) days (ratio of medians, 0.90; 95% confidence interval, 0.75 to 1.09; P = 0.27). Conclusions: In this large randomized controlled trial in adult ICU patients, a limited increase in the use of nursing interventions was achieved, and no change in the number of delirium-free and coma-free days alive in 28 days could be determined. Clinical trial registered with www.clinicaltrials.gov (NCT03002701).

Brain death/death by neurologic criteria determination: an update.

PURPOSE OF REVIEW: Brain death, also known as death by neurologic criteria (DNC), is a well-established concept. In this article, we present a short history of the concept and give an overview of recent changes and a practical update on diagnosis and definitions of brain death/DNC. Unresolved issues will be discussed. RECENT FINDINGS: There is variability in brain death/DNC determination worldwide. In recent years, successful attempts have been made to harmonize these criteria and, consequently, to improve public trust in the process and diagnosis. An international multidisciplinary collaboration has been created and it has published minimum criteria, provided guidance for professionals and encouragement to revise or develop guidelines on brain death/DNC worldwide. SUMMARY: There are two sets of criteria for declaration of death. First, if there is neither cardiac output nor respiratory effort, then cardiopulmonary criteria are used. Second, if both the cerebrum and brainstem have completely and permanently lost all functions, and there is a persistent coma, absent brainstem reflexes and no spontaneous respiratory effort, death can be declared on the basis of brain death/DNC. Although attempts to formulate uniform criteria are ongoing, consensus has been reached on the minimum criteria. Some inconsistencies and questions remain.

Prediction and Outcome of Intensive Care Unit-Acquired Paresis.

BACKGROUND: Intensive care unit-acquired paresis (ICUAP) is associated with poor outcomes. Our objective was to evaluate predictors for ICUAP and the short-term outcomes associated with this condition. METHODS: A secondary analysis of a prospective study including 4157 mechanically ventilated adults in 494 intensive care units from 39 countries. After sedative interruption, patients were screened for ICUAP daily, which was defined as the presence of symmetric and flaccid quadriparesis associated with decreased or absent deep tendon reflexes. A multinomial logistic regression was used to create a predictive model for ICUAP. Propensity score matching was used to estimate the relationship between ICUAP and short-term outcomes (ie, weaning failure and intensive care unit [ICU] mortality). RESULTS: Overall, 114 (3%) patients had ICUAP. Variables associated with ICUAP were duration of mechanical ventilation (relative risk ratio [RRR] per day, 1.10; 95% confidence interval [CI] 1.08-1.12), steroid therapy (RRR 1.8; 95% CI, 1.2-2.8), insulin therapy (RRR 1.8; 95% CI 1.2-2.7), sepsis (RRR 1.9; 95% CI: 1.2 to 2.9), acute renal failure (RRR 2.2; 95% CI 1.5-3.3), and hematological failure (RRR 1.9; 95% CI: 1.2-2.9). Coefficients were used to generate a weighted scoring system to predict ICUAP. ICUAP was significantly associated with both weaning failure (paired rate difference of 22.1%; 95% CI 9.8-31.6%) and ICU mortality (paired rate difference 10.5%; 95% CI 0.1-24.0%). CONCLUSIONS: Intensive care unit-acquired paresis is relatively uncommon but is significantly associated with weaning failure and ICU mortality. We constructed a weighted scoring system, with good discrimination, to predict ICUAP in mechanically ventilated patients at the time of awakening.

The impact of hospital and ICU organizational factors on outcome in critically ill patients: results from the Extended Prevalence of Infection in Intensive Care study.

OBJECTIVE: To investigate the impact of various facets of ICU organization on outcome in a large cohort of ICU patients from different geographic regions. DESIGN: International, multicenter, observational study. SETTING: All 1,265 ICUs in 75 countries that contributed to the 1-day point prevalence Extended Prevalence of Infection in Intensive Care study. PATIENTS: All adult patients present on a participating ICU on the study day. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The Extended Prevalence of Infection in Intensive Care study included data on 13,796 adult patients. Organizational characteristics of the participating hospitals and units varied across geographic areas. Participating North American hospitals had greater availability of microbiologic examination and more 24-hour emergency departments than did the participating European and Latin American units. Of the participating ICUs, 82.9% were closed format, with the lowest prevalence among North American units (62.7%) and the highest in ICUs in Oceania (92.6%). The proportion of participating ICUs with 24-hour intensivist coverage was lower in North America than in Latin America (86.8% vs 98.1%, p = 0.002). ICU volume was significantly lower in participating ICUs from Western Europe, Latin America, and Asia compared with North America. In multivariable logistic regression analysis, medical and mixed ICUs were independently associated with a greater risk of in-hospital death. A nurse:patient ratio of more than 1:1.5 on the study day was independently associated with a lower risk of in-hospital death. CONCLUSIONS: In this international large cohort of ICU patients, hospital and ICU characteristics varied worldwide. A high nurse:patient ratio was independently associated with a lower risk of in-hospital death. These exploratory data need to be confirmed in large prospective studies that consider additional country-specific ICU practice variations.

MicroRNAs: new biomarkers and therapeutic targets after cardiac arrest?

Despite advances in resuscitation medicine, including target temperature management as part of post-cardiac arrest care, many patients will have a poor neurological outcome, most often resulting in death. It is a commonly held belief that the ability to prognosticate outcome at an early stage after cardiac arrest would allow subsequent health care delivery to be tailored to individual patients. However, currently available predictive methods and biomarkers lack sufficient accuracy and therefore cannot be generally recommended in clinical practice. MicroRNAs have recently emerged as potential biomarkers of cardiovascular diseases. While the biomarker value of microRNAs for myocardial infarction or heart failure has been extensively studied, less attention has been devoted to their prognostic value after cardiac arrest. This review highlights the recent discoveries suggesting that microRNAs may be useful both to predict outcome and to treat patients after cardiac arrest.

Management and outcome of mechanically ventilated patients after cardiac arrest.

INTRODUCTION: The aim of this study was to describe and compare the changes in ventilator management and complications over time, as well as variables associated with 28-day hospital mortality in patients receiving mechanical ventilation (MV) after cardiac arrest. METHODS: We performed a secondary analysis of three prospective, observational multicenter studies conducted in 1998, 2004 and 2010 in 927 ICUs from 40 countries. We screened 18,302 patients receiving MV for more than 12 hours during a one-month-period. We included 812 patients receiving MV after cardiac arrest. We collected data on demographics, daily ventilator settings, complications during ventilation and outcomes. Multivariate logistic regression analysis was performed to calculate odds ratios, determining which variables within 24 hours of hospital admission were associated with 28-day hospital mortality and occurrence of acute respiratory distress syndrome (ARDS) and pneumonia acquired during ICU stay at 48 hours after admission. RESULTS: Among 812 patients, 100 were included from 1998, 239 from 2004 and 473 from 2010. Ventilatory management changed over time, with decreased tidal volumes (VT) (1998: mean 8.9 (standard deviation (SD) 2) ml/kg actual body weight (ABW), 2010: 6.7 (SD 2) ml/kg ABW; 2004: 9 (SD 2.3) ml/kg predicted body weight (PBW), 2010: 7.95 (SD 1.7) ml/kg PBW) and increased positive end-expiratory pressure (PEEP) (1998: mean 3.5 (SD 3), 2010: 6.5 (SD 3); P <0.001). Patients included from 2010 had more sepsis, cardiovascular dysfunction and neurological failure, but 28-day hospital mortality was similar over time (52% in 1998, 57% in 2004 and 52% in 2010). Variables independently associated with 28-day hospital mortality were: older age, PaO2 <60 mmHg, cardiovascular dysfunction and less use of sedative agents. Higher VT, and plateau pressure with lower PEEP were associated with occurrence of ARDS and pneumonia acquired during ICU stay. CONCLUSIONS: Protective mechanical ventilation with lower VT and higher PEEP is more commonly used after cardiac arrest. The incidence of pulmonary complications decreased, while other non-respiratory organ failures increased with time. The application of protective mechanical ventilation and the prevention of single and multiple organ failure may be considered to improve outcome in patients after cardiac arrest.

'Sepsis-related anemia' is absent at hospital presentation; a retrospective cohort analysis.

BACKGROUND: Anemia is a common feature during sepsis that occurs due to iatrogenic blood loss, depression of serum iron levels and erythropoietin production, and a decreased lifespan of erythrocytes. However, these mechanisms are unlikely to play a role in anemia at the start of sepsis. Moreover, sequestration of fluids, renal failure and increase of intravascular space may additionally influence the change in hemoglobin concentration during intravenous fluid administration in the acute phase of sepsis. METHODS: In this retrospective study, patients who were admitted acutely to the Intensive Care Unit (ICU) were included. Patients who fulfilled the international criteria for severe sepsis or septic shock were included in the sepsis group (S-group). The remaining patients were allocated to the control group (C-group). Laboratory data from blood samples taken at first presentation to the hospital and at admission to the ICU, the amount of intravenous fluid administration and length of stay in the emergency department were collected and tested for significant differences between groups. RESULTS: The difference in hemoglobin concentration between the S-group (n = 296) and C-group (n = 320) at first presentation in hospital was not significant (8.8 ± 1.2 versus 8.9 ± 1.2 mmol/l, respectively, p = 0.07). The reduction in hemoglobin concentration from the first presentation at the emergency department to ICU admission was significantly greater in the S-group compared to the C-group (1 [0.5-1.7] versus 0.5 [0.1-1.1] mmol/l, (p < 0.001)). Spearman rho correlation coefficients between the reduction in hemoglobin concentration and the amount of intravenous fluids administered or the creatinine level in the emergency department were significant (0.3 and 0.4, respectively, p < 0.001). In a multivariate regression analysis, creatinine, the amount of fluid administration and the presence of sepsis remained independently associated. CONCLUSIONS: Prior to in-hospital intravenous fluid administration, there is no significant difference in hemoglobin concentration between acute septic patients and acutely ill controls. Within several hours after hospital admission, there is a significant reduction in hemoglobin concentration, not only associated with the amount of intravenous fluids administered and the creatinine level, but also independently with sepsis itself.

Evolution of mortality over time in patients receiving mechanical ventilation.

RATIONALE: Baseline characteristics and management have changed over time in patients requiring mechanical ventilation; however, the impact of these changes on patient outcomes is unclear. OBJECTIVES: To estimate whether mortality in mechanically ventilated patients has changed over time. METHODS: Prospective cohort studies conducted in 1998, 2004, and 2010, including patients receiving mechanical ventilation for more than 12 hours in a 1-month period, from 927 units in 40 countries. To examine effects over time on mortality in intensive care units, we performed generalized estimating equation models. MEASUREMENTS AND MAIN RESULTS: We included 18,302 patients. The reasons for initiating mechanical ventilation varied significantly among cohorts. Ventilatory management changed over time (P < 0.001), with increased use of noninvasive positive-pressure ventilation (5% in 1998 to 14% in 2010), a decrease in tidal volume (mean 8.8 ml/kg actual body weight [SD = 2.1] in 1998 to 6.9 ml/kg [SD = 1.9] in 2010), and an increase in applied positive end-expiratory pressure (mean 4.2 cm H2O [SD = 3.8] in 1998 to 7.0 cm of H2O [SD = 3.0] in 2010). Crude mortality in the intensive care unit decreased in 2010 compared with 1998 (28 versus 31%; odds ratio, 0.87; 95% confidence interval, 0.80-0.94), despite a similar complication rate. Hospital mortality decreased similarly. After adjusting for baseline and management variables, this difference remained significant (odds ratio, 0.78; 95% confidence interval, 0.67-0.92). CONCLUSIONS: Patient characteristics and ventilation practices have changed over time, and outcomes of mechanically ventilated patients have improved. Clinical trials registered with www.clinicaltrials.gov (NCT01093482).

Influence of Two Colloidal Extracorporeal Primes on Coagulation of Cardiac Surgical Patients: A Prospectively Randomized Open-Label Pilot Trial.

The search for the ideal priming fluid continues as more evidence is discovered about side effects of volume expanders. With the availability of modern, balanced hydroxyethyl starch (HES) solutions with less side effects than former HES solutions, we considered to replace our gelatin- (modified gelatin) based extracorporeal circuit prime for a HES (130/.42) prime. Therefore, we studied the influence of two colloidal priming fluids on postoperative coagulation in patients undergoing cardiac surgery. The primary endpoint was to compare clot formation time between the HES group and the gelatin group with rotational thromboelastometry (ROTEM). Additionally we compared colloid osmotic pressure and fluid balance of both groups. Forty patients, undergoing elective first time coronary artery bypass grafting or single-valve surgery, were included in this prospectively randomized open-label pilot study. Laboratory data and ROTEM data were collected and analyzed for differences between the two groups. ROTEM data show significantly more prolongation in Extem clot formation time and significant more decrease in Extem alpha in the HES group. Fibtem maximum clot firmness was significantly smaller in the HES group; this was consistent with fibrinogen concentration measurement, which decreased more in the HES group than in the gelatin group and recovered more over time in the gelatin group. We found no significant difference in colloid. osmotic pressure between the groups. In this trial, HES (130/.42) impairs coagulation significantly more compared with gelatin. These differences in influence on coagulation did not lead to a difference in blood loss or fluid balance, so clinical relevance could not be proven.

Prognosis of coma after therapeutic hypothermia: a prospective cohort study.

OBJECTIVE: This study was designed to establish the reliability of neurologic examination, neuron-specific enolase (NSE), and median nerve somatosensory-evoked potentials (SEPs) to predict poor outcome in patients treated with mild hypothermia after cardiopulmonary resuscitation (CPR). METHODS: This multicenter prospective cohort study included adult comatose patients admitted to the intensive care unit (ICU) after CPR and treated with hypothermia (32-34°C). False-positive rates (FPRs 1 - specificity) with their 95% confidence intervals (CIs) were calculated for pupillary light responses, corneal reflexes, and motor scores 72 hours after CPR; NSE levels at admission, 12 hours after reaching target temperature, and 36 hours and 48 hours after collapse; and SEPs during hypothermia and after rewarming. The primary outcome was poor outcome, defined as death, vegetative state, or severe disability (Glasgow Outcome Scale 1-3) after 6 months. RESULTS: Of 391 patients included, 53% had a poor outcome. Absent pupillary light responses (FPR 1; 95% CI, 0-7) or absent corneal reflexes (FPR 4; 95% CI, 1-13) 72 hours after CPR, and absent SEPs during hypothermia (FPR 3; 95% CI, 1-7) and after rewarming (FPR 0; 95% CI, 0-18) were reliable predictors. Motor scores 72 hours after CPR (FPR 10; 95% CI, 6-16) and NSE levels were not. INTERPRETATION: In patients with persisting coma after CPR and therapeutic hypothermia, use of motor score or NSE, as recommended in current guidelines, could possibly lead to inappropriate withdrawal of treatment. Poor outcomes can reliably be predicted by testing brainstem reflexes 72 hours after CPR and performing SEP.

[Extracorporeal cardiopulmonary resuscitation in out-of-hospital resuscitation]. / Extracorporale cardiopulmonale resuscitatie bij reanimatie buiten het ziekenhuis.

If an out-of-hospital cardiac arrest (OHCA) takes longer than 15 minutes, the chances of survival are greatly reduced. With a shockable rhythm (VF/VT), there is often a treatable underlying cause, which most often can only be treated in a hospital. The patient can be transported, and circulation can be restored in the hospital, using extracorporeal cardiopulmonary resuscitation (ECPR) to gain time to treat the underlying problem. There are observational studies and one single-centre study that support the use of ECPR in refractory OHCA. However, two recent larger trials could not establish a significant benefit for ECPR. As many of these patients in refractory cardiac arrest will ultimately not survive, we will need solid cost-benefit analyses to evaluate the value of ECPR. We also need to explore the possibility of starting ECPR on scene, to reduce low-flow time even more, and hopefully improve the outcome of out-of-hospital cardiac arrest patients.

Femoral venous oxygen saturation is no surrogate for central venous oxygen saturation.

OBJECTIVE: The purpose of our study was to determine if central venous oxygen saturation and femoral venous oxygen saturation can be used interchangeably during surgery and in critically ill patients. DESIGN: Prospective observational controlled study. SETTING: Nonacademic university-affiliated teaching hospital in The Netherlands. PATIENTS: One hundred cardiac outpatients, 30 high-risk surgical patients, and 30 critically ill patients. INTERVENTIONS: None. METHODS AND MAIN RESULTS: We concurrently determined femoral venous oxygen saturation and central venous oxygen saturation in a group of 100 stable cardiac patients, which served as control group. Furthermore, we determined simultaneously femoral venous oxygen saturation and central venous oxygen saturation in 30 surgical patients and in 30 critically ill patients and evaluated changes over time. Correlation and agreement of femoral venous oxygen saturation and central venous oxygen saturation were assessed, including the difference between femoral venous oxygen saturation and central venous oxygen saturation.Despite significant correlation between obtained values of femoral venous oxygen saturation and central venous oxygen saturation (rs = 0.55; p < .001), the limits of agreement were wide in the control group (mean bias 2.7% ± 7.9%; 95% limits of agreement -12.9% to 18.2%). In both the surgical and critically ill patients, limits of agreement (mean bias of -1.9% ± 9.3%; 95% limits of agreement -20.0% to 16.3%, and mean bias of 4.6% ± 14.3%; 95% limits of agreement -23.5% to 32.6%, respectively) were wide. Results for changes of femoral venous oxygen saturation and central venous oxygen saturation were similar. During initial treatment of critically ill patients, the difference between femoral venous oxygen saturation and central venous oxygen saturation including its range of variation diminished. CONCLUSION: There is lack of agreement between femoral venous oxygen saturation and central venous oxygen saturation in both stable and unstable medical conditions. Thus, femoral venous oxygen saturation should not be used as surrogate for central venous oxygen saturation.

Acute posthypoxic myoclonus after cardiopulmonary resuscitation.

BACKGROUND: Acute posthypoxic myoclonus (PHM) can occur in patients admitted after cardiopulmonary resuscitation (CPR) and is considered to have a poor prognosis. The origin can be cortical and/or subcortical and this might be an important determinant for treatment options and prognosis. The aim of the study was to investigate whether acute PHM originates from cortical or subcortical structures, using somatosensory evoked potential (SEP) and electroencephalogram (EEG). METHODS: Patients with acute PHM (focal myoclonus or status myoclonus) within 72 hours after CPR were retrospectively selected from a multicenter cohort study. All patients were treated with hypothermia. Criteria for cortical origin of the myoclonus were: giant SEP potentials; or epileptic activity, status epilepticus, or generalized periodic discharges on the EEG (no back-averaging was used). Good outcome was defined as good recovery or moderate disability after 6 months. RESULTS: Acute PHM was reported in 79/391 patients (20%). SEPs were available in 51/79 patients and in 27 of them (53%) N20 potentials were present. Giant potentials were seen in 3 patients. EEGs were available in 36/79 patients with 23/36 (64%) patients fulfilling criteria for a cortical origin. Nine patients (12%) had a good outcome. A broad variety of drugs was used for treatment. CONCLUSIONS: The results of this study show that acute PHM originates from subcortical, as well as cortical structures. Outcome of patients admitted after CPR who develop acute PHM in this cohort was better than previously reported in literature. The broad variety of drugs used for treatment shows the existing uncertainty about optimal treatment.

Routine use of the confusion assessment method for the intensive care unit: a multicenter study.

RATIONALE: Delirium is often unrecognized in ICU patients and associated with poor outcome. Screening for ICU delirium is recommended by several medical organizations to improve early diagnosis and treatment. The Confusion Assessment Method for the ICU (CAM-ICU) has high sensitivity and specificity for delirium when administered by research nurses. However, test characteristics of the CAM-ICU as performed in routine practice are unclear. OBJECTIVES: To investigate the diagnostic value of the CAM-ICU in daily practice. METHODS: Teams of three delirium experts including psychiatrists, geriatricians, and neurologists visited 10 ICUs twice. Based on cognitive examination, inspection of medical files, and Diagnostic and Statistic Manual of Mental Disorders, 4th edition, Text Revision criteria for delirium, the expert teams classified patients as awake and not delirious, delirious, or comatose. This served as a gold standard to which the CAM-ICU as performed by the bedside ICU-nurses was compared. Assessors were unaware of each other's conclusions. MEASUREMENTS AND MAIN RESULTS: Fifteen delirium experts assessed 282 patients of whom 101 (36%) were comatose and excluded. In the remaining 181 (64%) patients, the CAM-ICU had a sensitivity of 47% (95% confidence interval [CI], 35%-58%); specificity of 98% (95% CI, 93%-100%); positive predictive value of 95% (95% CI, 80%-99%); and negative predictive value of 72% (95% CI, 64%-79%). The positive likelihood ratio was 24.7 (95% CI, 6.1-100) and the negative likelihood ratio was 0.5 (95% CI, 0.4-0.8). CONCLUSIONS: Specificity of the CAM-ICU as performed in routine practice seems to be high but sensitivity is low. This hampers early detection of delirium by the CAM-ICU.

Effect of rivastigmine as an adjunct to usual care with haloperidol on duration of delirium and mortality in critically ill patients: a multicentre, double-blind, placebo-controlled randomised trial.

BACKGROUND: Delirium is frequently diagnosed in critically ill patients and is associated with adverse outcome. Impaired cholinergic neurotransmission seems to have an important role in the development of delirium. We aimed to establish the effect of the cholinesterase inhibitor rivastigmine on the duration of delirium in critically ill patients. METHODS: Patients (aged ≥18 years) who were diagnosed with delirium were enrolled from six intensive care units in the Netherlands, and treated between November, 2008, and January, 2010. Patients were randomised (1:1 ratio) to receive an increasing dose of rivastigmine or placebo, starting at 0·75 mL (1·5 mg rivastigmine) twice daily and increasing in increments to 3 mL (6 mg rivastigmine) twice daily from day 10 onwards, as an adjunct to usual care based on haloperidol. The trial pharmacist generated the randomisation sequence by computer, and consecutively numbered bottles of the study drug according to this sequence to conceal allocation. The primary outcome was the duration of delirium during hospital admission. Analysis was by intention to treat. Duration of delirium was censored for patients who died or were discharged from hospital while delirious. Patients, medical staff, and investigators were masked to treatment allocation. Members of the data safety and monitoring board (DSMB) were unmasked and did interim analyses every 3 months. This trial is registered with ClinicalTrials.gov, number NCT00704301. FINDINGS: Although a sample size of 440 patients was planned, after inclusion of 104 patients with delirium who were eligible for the intention-to-treat analysis (n=54 on rivastigmine, n=50 on placebo), the DSMB recommended that the trial be halted because mortality in the rivastigmine group (n=12, 22%) was higher than in the placebo group (n=4, 8%; p=0·07). Median duration of delirium was longer in the rivastigmine group (5·0 days, IQR 2·7-14·2) than in the placebo group (3·0 days, IQR 1·0-9·3; p=0·06). INTERPRETATION: Rivastigmine did not decrease duration of delirium and might have increased mortality so we do not recommend use of rivastigmine to treat delirium in critically ill patients. FUNDING: ZonMw, the Netherlands Brain Foundation, and Novartis.

Effects of nitroglycerin on sublingual microcirculatory blood flow in patients with severe sepsis/septic shock after a strict resuscitation protocol: a double-blind randomized placebo controlled trial.

OBJECTIVES: Microcirculatory alterations have been associated with morbidity and mortality in human sepsis. Such alterations occur despite pressure-guided resuscitation. Earlier data suggested that impaired microcirculatory blood flow could be corrected with intravenous nitroglycerin in these patients. We tested this concept after fulfillment of preset systemic hemodynamic resuscitation end points in the early phase of sepsis. DESIGN: Prospective, single center, randomized, placebo-controlled, double-blind clinical trial. SETTING: Closed-format 22-bed mixed intensive care unit in a tertiary teaching hospital. PATIENTS: Patients > or =18 yrs with sepsis, according to international criteria, and at least one early sign of organ dysfunction, as the principal reason for intensive care unit admission, were eligible for enrollment. INTERVENTIONS: Patients were randomly assigned to receive nitroglycerin (n = 35) or placebo (n = 35) after fulfillment of protocol-driven resuscitation end points. This trial is registered with ClinicalTrials.gov as NCT00493415. MEASUREMENTS AND MAIN RESULTS: Primary outcome was sublingual microcirculatory blood flow of small vessels, as assessed by side-stream dark field imaging. After protocolized resuscitation, we observed recruitment of sublingual microcirculation in both groups, as indicated by a significant improvement in the microcirculatory flow index after 24 hrs, in comparison to baseline. However, no difference in the sublingual microvascular flow index was observed between groups. The median microvascular flow index in sublingual small-sized vessels was 2.71 (1.85-3) in the nitroglycerin group and 2.71 (1.27-3), p = .80, in the placebo group. In medium-sized vessels, the respective values were 3 (2.75-3) vs. 2.86 (2.19-3), p = .21, and in large-sized vessels, 3 (3-3) vs. 3 (2.89-3), p = .06. In-hospital mortality, as a secondary outcome, was 34.3% in the nitroglycerin group and 14.2% in the placebo group, p = .09. CONCLUSIONS: In the context of a strict resuscitation protocol, based upon fulfillment of systemic hemodynamic end points in patients with early-phase severe sepsis or septic shock, we conclude that intravenous nitroglycerin does not promote sublingual microcirculatory blood flow.

Treatment of hypophosphatemia in the intensive care unit: a review.

INTRODUCTION: Currently no evidence-based guideline exists for the approach to hypophosphatemia in critically ill patients. METHODS: We performed a narrative review of the medical literature to identify the incidence, symptoms, and treatment of hypophosphatemia in critically ill patients. Specifically, we searched for answers to the questions whether correction of hypophosphatemia is associated with improved outcome, and whether a certain treatment strategy is superior. RESULTS: Incidence: hypophosphatemia is frequently encountered in the intensive care unit; and critically ill patients are at increased risk for developing hypophosphatemia due to the presence of multiple causal factors. SYMPTOMS: hypophosphatemia may lead to a multitude of symptoms, including cardiac and respiratory failure. TREATMENT: hypophosphatemia is generally corrected when it is symptomatic or severe. However, although multiple studies confirm the efficacy and safety of intravenous phosphate administration, it remains uncertain when and how to correct hypophosphatemia. OUTCOME: in some studies, hypophosphatemia was associated with higher mortality; a paucity of randomized controlled evidence exists for whether correction of hypophosphatemia improves the outcome in critically ill patients. CONCLUSIONS: Additional studies addressing the current approach to hypophosphatemia in critically ill patients are required. Studies should focus on the association between hypophosphatemia and morbidity and/or mortality, as well as the effect of correction of this electrolyte disorder.

No agreement of mixed venous and central venous saturation in sepsis, independent of sepsis origin.

INTRODUCTION: Controversy remains regarding the relationship between central venous saturation (ScvO(2)) and mixed venous saturation (SvO(2)) and their use and interchangeability in patients with sepsis or septic shock. We tested the hypothesis that ScvO(2) does not reliably predict SvO(2) in sepsis. Additionally we looked at the influence of the source (splanchnic or non-splanchnic) of sepsis on this relationship. METHODS: In this prospective observational two-center study we concurrently determined ScvO(2) and SvO(2) in a group of 53 patients with severe sepsis during the first 24 hours after admission to the intensive care units in 2 Dutch hospitals. We assessed correlation and agreement of ScvO(2) and SvO(2), including the difference, i.e. the gradient, between ScvO(2) and SvO(2) (ScvO(2) - SvO(2)). Additionally, we compared the mean differences between ScvO(2) and SvO(2) of both splanchnic and non-splanchnic group. RESULTS: A total of 265 paired blood samples were obtained. ScvO(2) overestimated SvO(2) by less than 5% with wide limits of agreement. For changes in ScvO(2) and SvO(2) results were similar. The distribution of the (ScvO(2) - SvO(2)) (< 0 or ≥ 0) was similar in survivors and nonsurvivors. The mean (ScvO(2) - SvO(2)) in the splanchnic group was similar to the mean (ScvO(2) - SvO(2)) in the non-splanchnic group (0.8 ± 3.9% vs. 2.5 ± 6.2%; P = 0.30). O(2)ER (P = 0.23) and its predictive value for outcome (P = 0.20) were similar in both groups. CONCLUSIONS: ScvO(2) does not reliably predict SvO(2) in patients with severe sepsis. The trend of ScvO(2) is not superior to the absolute value in this context. A positive difference (ScvO(2) - SvO(2)) is not associated with improved outcome.