Nutrition intervention for migraine: a randomized crossover trial

Background

Limited evidence suggests that dietary interventions may offer a promising approach for migraine. The purpose of this study was to determine the effects of a low-fat plant-based diet intervention on migraine severity and frequency.

Methods

Forty-two adult migraine sufferers were recruited from the general community in Washington, DC, and divided randomly into two groups. This 36-week crossover study included two treatments: dietary instruction and placebo supplement. Each treatment period was 16 weeks, with a 4-week washout between. During the diet period, a low-fat vegan diet was prescribed for 4 weeks, after which an elimination diet was used. Participants were assessed at the beginning, midpoint, and end of each period. Significance was determined using student’s t-tests.

Results

Worst headache pain in last 2 weeks, as measured by visual analog scale, was initially 6.4/10 cm (SD 2.1 cm), and declined 2.1 cm during the diet period and 0.7 cm during the supplement period (p=0.03). Average headache intensity (0–10 scale) was initially 4.2 (SD 1.4) per week, and this declined by 1.0 during the diet period and by 0.5 during the supplement period (p=0.20). Average headache frequency was initially 2.3 (SD 1.8) per week, and this declined by 0.3 during the diet period and by 0.4 during the supplement period (p=0.61). The Patient’s Global Impression of Change showed greater improvement in pain during the diet period (p<0.001).

Conclusions

These results suggest that a nutritional approach may be a useful part of migraine treatment, but that methodologic issues necessitate further research.

Trial registration

Clinicaltrials.gov, {"type":"clinical-trial","attrs":{"text":"NCT01699009","term_id":"NCT01699009"}}NCT01699009 and {"type":"clinical-trial","attrs":{"text":"NCT01547494","term_id":"NCT01547494"}}NCT01547494.     

Intravenous angiotensin II for the treatment of high-output shock (ATHOS trial): a pilot study

Introduction

Patients with distributive shock who require high dose vasopressors have a high mortality. Angiotensin II (ATII) may prove useful in patients who remain hypotensive despite catecholamine and vasopressin therapy. The appropriate dose of parenteral angiotensin II for shock is unknown.

Methods

In total, 20 patients with distributive shock and a cardiovascular Sequential Organ Failure Assessment score of 4 were randomized to either ATII infusion (N =10) or placebo (N =10) plus standard of care. ATII was started at a dose of 20 ng/kg/min, and titrated for a goal of maintaining a mean arterial pressure (MAP) of 65 mmHg. The infusion (either ATII or placebo) was continued for 6 hours then titrated off. The primary endpoint was the effect of ATII on the standing dose of norepinephrine required to maintain a MAP of 65 mmHg.

Results

ATII resulted in marked reduction in norepinephrine dosing in all patients. The mean hour 1 norepinephrine dose for the placebo cohort was 27.6 ± 29.3 mcg/min versus 7.4 ± 12.4 mcg/min for the ATII cohort (P =0.06). The most common adverse event attributable to ATII was hypertension, which occurred in 20% of patients receiving ATII. 30-day mortality for the ATII cohort and the placebo cohort was similar (50% versus 60%, P =1.00).

Conclusion

Angiotensin II is an effective rescue vasopressor agent in patients with distributive shock requiring multiple vasopressors. The initial dose range of ATII that appears to be appropriate for patients with distributive shock is 2 to 10 ng/kg/min.

Trial registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01393782","term_id":"NCT01393782"}}NCT01393782. Registered 12 July 2011.     

The association between cardiovascular risk and cardiovascular magnetic resonance measures of fibrosis: the Multi-Ethnic Study of Atherosclerosis (MESA)

Background

Risk scores for cardiovascular disease (CVD) are in common use to integrate multiple cardiovascular risk factors in order to identify individuals at greatest risk for disease. The purpose of this study was to determine if individuals at greater cardiovascular risk have T₁ mapping indices by cardiovascular magnetic resonance (CMR) indicative of greater myocardial fibrosis.

Methods

CVD risk scores for 1208 subjects (men, 50.8%) ages 55–94 years old were evaluated in the Multiethnic Study of Atherosclerosis (MESA) at six centers. T₁ times were determined at 1.5Tesla before and after gadolinium administration (0.15 mmol/kg) using a modified Look-Locker pulse sequence. The relationship between CMR measures (native T₁, 12 and 25 minute post-gadolinium T₁, partition coefficient and extracellular volume fraction) and 14 established different cardiovascular risk scores were determined using regression analysis. Bootstrapping analysis with analysis of variance was used to compare different CMR measures. CVD risk scores were significantly different for men and women (p < 0.001).

Results

25 minute post gadolinium T₁ time showed more statistically significant associations with risk scores (10/14 scores, 71%) compared to other CMR indices (e.g. native T₁ (7/14 scores, 50%) and partition coefficient (7/14, 50%) in men. Risk scores, particularly the new 2013 AHA/ASCVD risk score, did not correlate with any CMR fibrosis index.

Conclusions

Men with greater CVD risk had greater CMR indices of myocardial fibrosis. T₁ times at greater delay time (25 minutes) showed better agreement with commonly used risk score indices compared to ECV and native T₁ time.

Clinical trial registration

http://www.mesa-nhlbi.org/, {"type":"clinical-trial","attrs":{"text":"NCT00005487","term_id":"NCT00005487"}}NCT00005487.     

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     

Short-term effects of noisy pressure support ventilation in patients with acute hypoxemic respiratory failure

Introduction

This study aims at comparing the very short-term effects of conventional and noisy (variable) pressure support ventilation (PSV) in mechanically ventilated patients with acute hypoxemic respiratory failure.

Methods

Thirteen mechanically ventilated patients with acute hypoxemic respiratory failure were enrolled in this monocentric, randomized crossover study. Patients were mechanically ventilated with conventional and noisy PSV, for one hour each, in random sequence. Pressure support was titrated to reach tidal volumes approximately 8 mL/kg in both modes. The level of positive end-expiratory pressure and fraction of inspired oxygen were kept unchanged in both modes. The coefficient of variation of pressure support during noisy PSV was set at 30%. Gas exchange, hemodynamics, lung functional parameters, distribution of ventilation by electrical impedance tomography, breathing patterns and patient-ventilator synchrony were analyzed.

Results

Noisy PSV was not associated with any adverse event, and was well tolerated by all patients. Gas exchange, hemodynamics, respiratory mechanics and spatial distribution of ventilation did not differ significantly between conventional and noisy PSV. Noisy PSV increased the variability of tidal volume (24.4 ± 7.8% vs. 13.7 ± 9.1%, P <0.05) and was associated with a reduced number of asynchrony events compared to conventional PSV (5 (0 to 15)/30 min vs. 10 (1 to 37)/30 min, P <0.05).

Conclusions

In the very short term, noisy PSV proved safe and feasible in patients with acute hypoxemic respiratory failure. Compared to conventional PSV, noisy PSV increased the variability of tidal volumes, and was associated with improved patient-ventilator synchrony, at comparable levels of gas exchange.

Trial registration

ClinicialTrials.gov, {"type":"clinical-trial","attrs":{"text":"NCT00786292","term_id":"NCT00786292"}}NCT00786292     

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     

Effect of erythropoietin on the incidence of acute kidney injury following complex valvular heart surgery: a double blind,randomized clinical trial of efficacy and safety

Introduction

Recombinant human erythropoietin (EPO) is known to provide organ protection against ischemia-reperfusion injury through its pleiotropic properties. The aim of this single-site, randomized, case-controlled, and double-blind study was to investigate the effect of pre-emptive EPO administration on the incidence of postoperative acute kidney injury (AKI) in patients with risk factors for AKI undergoing complex valvular heart surgery.

Methods

We studied ninety-eight patients with preoperative risk factors for AKI. The patients were randomly allocated to either the EPO group (n = 49) or the control group (n = 49). The EPO group received 300 IU/kg of EPO intravenously after anesthetic induction. The control group received an equivalent volume of normal saline. AKI was defined as an increase in serum creatinine >0.3 mg/dl or >50% from baseline. Biomarkers of renal injury were serially measured until five days postoperatively.

Results

Patient characteristics and operative data, including the duration of cardiopulmonary bypass, were similar between the two groups. Incidence of postoperative AKI (32.7% versus 34.7%, P = 0.831) and biomarkers of renal injury including cystatin C and neutrophil gelatinase-associated lipocalin showed no significant differences between the groups. The postoperative increase in interleukin-6 and myeloperoxidase was similar between the groups. None of the patients developed adverse complications related to EPO administration, including thromboembolic events, throughout the study period.

Conclusions

Intravenous administration of 300 IU/kg of EPO did not provide renal protection in patients who are at increased risk of developing AKI after undergoing complex valvular heart surgery.

Trial registration

Clinical Trial.gov, {"type":"clinical-trial","attrs":{"text":"NCT01758861","term_id":"NCT01758861"}}NCT01758861     

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).     

Early treatment with IgM-enriched intravenous immunoglobulin does not mitigate critical illness polyneuropathy and/or myopathy in patients with multiple organ failure and SIRS/sepsis: a prospective,randomized, placebo-controlled,double-blinded trial

Introduction

Critical illness polyneuropathy and/or myopathy (CIPNM) is a severe complication of critical illness. Retrospective data suggest that early application of IgM-enriched intravenous immunoglobulin (IVIG) may prevent or mitigate CIPNM. Therefore, the primary objective was to assess the effect of early IgM-enriched IVIG versus placebo to mitigate CIPNM in a prospective setting.

Methods

In this prospective, randomized, double-blinded and placebo-controlled trial, 38 critically ill patients with multiple organ failure (MOF), systemic inflammatory response syndrome (SIRS)/sepsis, and early clinical signs of CIPNM were included. Patients were randomly assigned to be treated either with IgM-enriched IVIG or placebo over a period of three days. CIPNM was measured by the CIPNM severity sum score based on electrophysiological stimulation of the median, ulnar, and tibial nerves on days 0, 4, 7, 14 and on the histological evaluation of muscle biopsies on days 0 and 14 and ranged from 0 (no CIPNM) to 8 (very severe CIPNM).

Results

A total of 38 critically ill patients were included and randomized to receive either IgM-enriched IVIG (n = 19) or placebo (n = 19). Baseline characteristics were similar between the two groups. CIPNM could not be improved by IVIG treatment, represented by similar CIPNM severity sum scores on day 14 (IVIG vs. placebo: 4.8 ± 2.0 vs. 4.5 ± 1.8; P = 0.70). CIPNM severity sum score significantly increased from baseline to day 14 (3.5 ± 1.6 vs. 4.6 ± 1.9; P = 0.002). After an interim analysis the study was terminated early due to futility in reaching the primary endpoint.

Conclusions

Early treatment with IVIG did not mitigate CIPNM in critically ill patients with MOF and SIRS/sepsis.

Trial registration

Clinicaltrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT01867645","term_id":"NCT01867645"}}NCT01867645     

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     

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.     

Optimal Mode of clearance in critically ill patients with Acute Kidney Injury (OMAKI) - a pilot randomized controlled trial of hemofiltration versus hemodialysis: a Canadian Critical Care Trials Group project

Introduction

Among critically ill patients with acute kidney injury (AKI) needing continuous renal replacement therapy (CRRT), the effect of convective (via continuous venovenous hemofiltration [CVVH]) versus diffusive (via continuous venovenous hemodialysis [CVVHD]) solute clearance on clinical outcomes is unclear. Our objective was to evaluate the feasibility of comparing these two modes in a randomized trial.

Methods

This was a multicenter open-label parallel-group pilot randomized trial of CVVH versus CVVHD. Using concealed allocation, we randomized critically ill adults with AKI and hemodynamic instability to CVVH or CVVHD, with a prescribed small solute clearance of 35 mL/kg/hour in both arms. The primary outcome was trial feasibility, defined by randomization of >25% of eligible patients, delivery of >75% of the prescribed CRRT dose, and follow-up of >95% of patients to 60 days. A secondary analysis using a mixed-effects model examined the impact of therapy on illness severity, defined by sequential organ failure assessment (SOFA) score, over the first week.

Results

We randomized 78 patients (mean age 61.5 years; 39% women; 23% with chronic kidney disease; 82% with sepsis). Baseline SOFA scores (mean 15.9, SD 3.2) were similar between groups. We recruited 55% of eligible patients, delivered >80% of the prescribed dose in each arm, and achieved 100% follow-up. SOFA tended to decline more over the first week in CVVH recipients (-0.8, 95% CI -2.1, +0.5) driven by a reduction in vasopressor requirements. Mortality (54% CVVH; 55% CVVHD) and dialysis dependence in survivors (24% CVVH; 19% CVVHD) at 60 days were similar.

Conclusions

Our results suggest that a large trial comparing CVVH to CVVHD would be feasible. There is a trend toward improved vasopressor requirements among CVVH-treated patients over the first week of treatment.

Trial Registration

ClinicalTrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT00675818","term_id":"NCT00675818"}}NCT00675818     

Left ventricular global function index assessed by cardiovascular magnetic resonance for the prediction of cardiovascular events in ST-elevation myocardial infarction

Background

The left ventricular performance index (LVGFI) as a comprehensive marker of cardiac performance integrates LV structure with global function within one index. In a prospective cohort study of healthy individuals the LVGFI demonstrated a superior prognostic value as compared to LV ejection fraction (LVEF). In patients after ST-segment elevation myocardial infarction (STEMI), however, the role of the LVGFI is unknown. Aim of this study was to investigate the relationship between the LVGFI and infarct characteristics as well as prognosis in a large multicenter STEMI population.

Methods

In total 795 STEMI patients reperfused by primary angioplasty (<12 h after symptom onset) underwent cardiovascular magnetic resonance (CMR) at 8 centers. CMR was completed within one week after infarction using a standardized protocol including LV dimensions, mass and function for calculation of the LVGFI. The primary clinical endpoint of the study was the occurrence of major adverse cardiac events (MACE).

Results

The median LVGFI was 31.2 % (interquartile range 25.7 to 36.6). Patients with LVGFI < median had significantly larger infarcts, less myocardial salvage, a larger extent of microvascular obstruction, higher incidence of intramyocardial hemorrhage and more pronounced LV dysfunction (p < 0.001 for all). MACE and mortality rates were significantly higher in the LVGFI < median group (p < 0.001 and p = 0.003, respectively). The LVGFI had an incremental prognostic value in addition to LVEF for prediction of all-cause mortality.

Conclusions

The LVGFI strongly correlates with markers of severe myocardial and microvascular damage in patients with STEMI, offering prognostic information beyond traditional cardiac risk factors including the LVEF.

Trials registration

ClinicalTrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT00712101","term_id":"NCT00712101"}}NCT00712101     

Considerations when measuring myocardial perfusion reserve by cardiovascular magnetic resonance using regadenoson

Background

Adenosine cardiovascular magnetic resonance (CMR) can accurately quantify myocardial perfusion reserve. While regadenoson is increasingly employed due to ease of use, imaging protocols have not been standardized. We sought to determine the optimal regadenoson CMR protocol for quantifying myocardial perfusion reserve index (MPRi) – more specifically, whether regadenoson stress imaging should be performed before or after rest imaging.

Methods

Twenty healthy subjects underwent CMR perfusion imaging during resting conditions, during regadenoson-induced hyperemia (0.4 mg), and after 15 min of recovery. In 10/20 subjects, recovery was facilitated with aminophylline (125 mg). Myocardial time-intensity curves were used to obtain left ventricular cavity-normalized myocardial up-slopes. MPRi was calculated in two different ways: as the up-slope ratio of stress to rest (MPRi-rest), and the up-slope ratio of stress to recovery (MPRi-recov).

Results

In all 20 subjects, MPRi-rest was 1.78 ± 0.60. Recovery up-slope did not return to resting levels, regardless of aminophylline use. Among patients not receiving aminophylline, MPRi-recov was 36 ± 16% lower than MPRi-rest (1.13 ± 0.38 vs. 1.82 ± 0.73, P = 0.001). In the 10 patients whose recovery was facilitated with aminophylline, MPRi-recov was 20 ± 24% lower than MPRi-rest (1.40 ± 0.35 vs. 1.73 ± 0.43, P = 0.04), indicating incomplete reversal. In 3 subjects not receiving aminophylline and 4 subjects receiving aminophylline, up-slope at recovery was greater than at stress, suggesting delayed maximal hyperemia.

Conclusions

MPRi measurements from regadenoson CMR are underestimated if recovery perfusion is used as a substitute for resting perfusion, even when recovery is facilitated with aminophylline. True resting images should be used to allow accurate MPRi quantification. The delayed maximal hyperemia observed in some subjects deserves further study.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00871260","term_id":"NCT00871260"}}NCT00871260     

Screening and risk factors of exocrine pancreatic insufficiency in critically ill adult patients receiving enteral nutrition

Introduction

Malnutrition is a frequent problem associated with detrimental clinical outcomes in critically ill patients. To avoid malnutrition, most studies focus on the prevention of inadequate nutrition delivery, whereas little attention is paid to the potential role of exocrine pancreatic insufficiency (EPI). In this trial, we aim to evaluate the prevalence of EPI and identify its potential risk factors in critically ill adult patients without preexisting pancreatic diseases.

Methods

In this prospective cross-sectional study, we recruited 563 adult patients with critical illnesses. All details of the patients were documented, stool samples were collected three to five days following the initiation of enteral nutrition, and faecal elastase 1 (FE-1) concentrations were assayed using an enzyme-linked immunosorbent assay kit. Blood samples were also taken to determine serum amylase and lipase activity.

Results

The percentages of recruited patients with EPI (FE-1 concentration <200 μg/g) and severe EPI (FE-1 concentration <100 μg/g) were 52.2% and 18.3%, respectively. The incidences of steatorrhea were significantly different (P < 0.05) among the patients without EPI, with moderate EPI (FE-1 concentration = 100 to 200 μg/g) and severe EPI (FE-1 concentration < 100 μg/g). Both multivariate logistic regression analysis and z-tests indicated that the occurrence of EPI was closely associated with shock, sepsis, diabetes, cardiac arrest, hyperlactacidemia, invasive mechanical ventilation and haemodialysis.

Conclusions

More than 50% of critically ill adult patients without primary pancreatic diseases had EPI, and nearly one-fifth of them had severe EPI. The risk factors for EPI included shock, sepsis, diabetes, cardiac arrest, hyperlactacidemia, invasive mechanical ventilation and haemodialysis.

Trial registration

{"type":"clinical-trial","attrs":{"text":"NCT01753024","term_id":"NCT01753024"}}NCT01753024     

Feasibility of fully automated closed-loop glucose control using continuous subcutaneous glucose measurements in critical illness: a randomized controlled trial

Introduction

Closed-loop (CL) systems modulate insulin delivery according to glucose levels without nurse input. In a prospective randomized controlled trial, we evaluated the feasibility of an automated closed-loop approach based on subcutaneous glucose measurements in comparison with a local sliding-scale insulin-therapy protocol.

Methods

Twenty-four critically ill adults (predominantly trauma and neuroscience patients) with hyperglycemia (glucose, ≥10 mM) or already receiving insulin therapy, were randomized to receive either fully automated closed-loop therapy (model predictive control algorithm directing insulin and 20% dextrose infusion based on FreeStyle Navigator continuous subcutaneous glucose values, n = 12) or a local protocol (n = 12) with intravenous sliding-scale insulin, over a 48-hour period. The primary end point was percentage of time when arterial blood glucose was between 6.0 and 8.0 mM.

Results

The time when glucose was in the target range was significantly increased during closed-loop therapy (54.3% (44.1 to 72.8) versus 18.5% (0.1 to 39.9), P = 0.001; median (interquartile range)), and so was time in wider targets, 5.6 to 10.0 mM and 4.0 to 10.0 mM (P ≤ 0.002), reflecting a reduced glucose exposure >8 and >10 mM (P ≤ 0.002). Mean glucose was significantly lower during CL (7.8 (7.4 to 8.2) versus 9.1 (8.3 to 13.0] mM; P = 0.001) without hypoglycemia (<4 mM) during either therapy.

Conclusions

Fully automated closed-loop control based on subcutaneous glucose measurements is feasible and may provide efficacious and hypoglycemia-free glucose control in critically ill adults.

Trial Registration

ClinicalTrials.gov Identifier, {"type":"clinical-trial","attrs":{"text":"NCT01440842","term_id":"NCT01440842"}}NCT01440842.     

PINOT NOIR: Pulmonic INsufficiency imprOvemenT with Nitric Oxide Inhalational Response

Background

Tetralogy of Fallot (TOF) repair and pulmonary valvotomy for pulmonary stenosis (PS) lead to progressive pulmonary insufficiency (PI), right ventricular enlargement and dysfunction. This study assessed whether pulmonary regurgitant fraction measured by cardiovascular magnetic resonance (CMR) could be reduced with inhaled nitric oxide (iNO).

Methods

Patients with at least moderate PI by echocardiography undergoing clinically indicated CMR were prospectively enrolled. Patients with residual hemodynamic lesions were excluded. Ventricular volume and blood flow sequences were obtained at baseline and during administration of 40 ppm iNO.

Results

Sixteen patients (11 with repaired TOF and 5 with repaired PS) completed the protocol with adequate data for analysis. The median age [range] was 35 [19–46] years, BMI was 26 ± 5 kg/m² (mean ± SD), 50% were women and 75% were in NYHA class I. Right ventricular end diastolic volume index for the cohort was 157 ± 33 mL/m², end systolic volume index was 93 ± 20 mL/m² and right ventricular ejection fraction was 40 ± 6%. Baseline pulmonary regurgitant volume was 45 ± 25 mL/beat and regurgitant fraction was 35 ± 16%. During administration of iNO, regurgitant volume was reduced by an average of 6 ± 9% (p=0.01) and regurgitant fraction was reduced by an average of 5 ± 8% (p=0.02). No significant changes were observed in ventricular indices for either the left or right ventricle.

Conclusion

iNO was successfully administered during CMR acquisition and appears to reduce regurgitant fraction in patients with at least moderate PI suggesting a potential role for selective pulmonary vasodilator therapy in these patients.

Trials registration

ClinicalTrials.gov, {"type":"clinical-trial","attrs":{"text":"NCT00543933","term_id":"NCT00543933"}}NCT00543933     

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     

Impairment of cardiac metabolism and sympathetic innervation after aneurysmal subarachnoid hemorrhage: a nuclear medicine imaging study

Introduction

Although aneurysmal subarachnoid hemorrhage (SAH) is often complicated by myocardial injury, whether this neurogenic cardiomyopathy is associated with the modification of cardiac metabolism is unknown. This study sought to explore, by positron emission tomography/computed tomography, the presence of altered cardiac glucose metabolism after SAH.

Methods

During a 16-month period, 30 SAH acute phase patients underwent myocardial ¹⁸ F- fluorodesoxyglucose positron emission tomography (¹⁸F-FDGPET), ^99mTc-tetrofosmin and ¹²³I-meta-iodobenzylguanidine (¹²³I-mIBG) scintigraphy, respectively, assessing glucose metabolism, cardiac perfusion, and sympathetic innervation. Patients with initial abnormalities were followed monthly for two months for ¹⁸F-FDG, and six months later for ¹²³I-mIBG.

Results

In this SAH population, acute cardiac metabolic disturbance was observed in 83% of patients (n = 25), and sympathetic innervation disturbance affected 90% (n = 27). Myocardial perfusion was normal for all patients. The topography and extent of metabolic defects and innervation abnormalities largely overlapped. Follow-up showed rapid improvement of glucose metabolism in one or two months. Normalization of sympathetic innervation was slower; only 27% of patients (n = 8) exhibited normal ¹²³I-mIBG scintigraphy after six months. Presence of initial altered cardiac metabolism was not associated with more unfavorable cardiac or neurological outcomes.

Conclusions

These findings support the hypothesis of neurogenic myocardial stunning after SAH. In hemodynamically stable acute phase SAH patients, cardiomyopathy is characterized by diffuse and heterogeneous ¹⁸F-FDG and ¹²³I-mIBG uptake defect.

Trial registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01218191","term_id":"NCT01218191"}}NCT01218191. Registered 6 October 2010.     

Mechanism of action of tranexamic acid in bleeding trauma patients: an exploratory analysis of data from the CRASH-2 trial

Introduction

To investigate the mechanism of action of tranexamic acid (TXA) in bleeding trauma patients, we examined the timing of its effect on mortality. We hypothesised that if TXA reduces mortality by decreasing blood loss, its effect should be greatest on the day of the injury when bleeding is most profuse. However, if TXA reduces mortality via an anti-inflammatory mechanism its effect should be greater over the subsequent days.

Methods

Exploratory analysis, including per-protocol analyses, of data from the CRASH-2 trial, a randomised placebo controlled trial of the effect of TXA on mortality in 20,211 trauma patients with, or at risk of, significant bleeding. We examined hazard ratios (HR) and 95% confidence intervals for all-cause mortality, deaths due to bleeding and non-bleeding deaths, according to the day since injury. The CRASH-2 trial is registered as ISRCTN86750102 and ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00375258","term_id":"NCT00375258"}}NCT00375258.

Results

The effect of TXA on mortality is greatest for deaths occurring on the day of the injury (HR all-cause mortality = 0.83, 0.73 to 0.93). This survival benefit is only evident in patients in whom treatment is initiated within 3 hours of their injury (HR ≤3 hours = 0.78, 0.68 to 0.90; HR >3 hours = 1.02, 0.76 to 1.36). Initiation of TXA treatment within 3 hours of injury reduced the hazard of death due to bleeding on the day of the injury by 28% (HR = 0.72, 0.60 to 0.86). TXA treatment initiated beyond 3 hours of injury appeared to increase the hazard of death due to bleeding, although the estimates were imprecise.

Conclusions

Early administration of tranexamic acid appears to reduce mortality primarily by preventing exsanguination on the day of the injury.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-014-0685-8) contains supplementary material, which is available to authorized users.