Assessment of Right Ventricle Function and Tricuspid Regurgitation in Heart Failure: Current Advances in Diagnosis and Imaging.

Right ventricular (RV) systolic dysfunction increases mortality among heart failure patients, and therefore, accurate diagnosis and monitoring is paramount. RV anatomy and function are complex, usually requiring a combination of imaging modalities to completely quantitate volumes and function. Tricuspid regurgitation usually occurs with RV dysfunction, and quantifying this valvular lesion also may require multiple imaging modalities. Echocardiography is the first-line imaging tool for identifying RV dysfunction, with cardiac MRI and cardiac computed tomography adding valuable additional information.

Impact of renin-angiotensin-aldosterone system inhibition on mortality in critically ill COVID-19 patients with pre-existing hypertension: a prospective cohort study.

BACKGROUND: The influence of renin-angiotensin-aldosterone system (RAAS) inhibitors on the critically ill COVID-19 patients with pre-existing hypertension remains uncertain. This study examined the impact of previous use of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) on the critically ill COVID-19 patients. METHODS: Data from an international, prospective, observational cohort study involving 354 hospitals spanning 54 countries were included. A cohort of 737 COVID-19 patients with pre-existing hypertension admitted to intensive care units (ICUs) in 2020 were targeted. Multi-state survival analysis was performed to evaluate in-hospital mortality and hospital length of stay up to 90 days following ICU admission. RESULTS: A total of 737 patients were included-538 (73%) with pre-existing hypertension had received ACEi/ARBs before ICU admission, while 199 (27%) had not. Cox proportional hazards model showed that previous ACEi/ARB use was associated with a decreased hazard of in-hospital death (HR, 0.74, 95% CI 0.58-0.94). Sensitivity analysis adjusted for propensity scores showed similar results for hazards of death. The average length of hospital stay was longer in ACEi/ARB group with 21.2 days (95% CI 19.7-22.8 days) in ICU and 6.7 days (5.9-7.6 days) in general ward compared to non-ACEi/ARB group with 16.2 days (14.1-18.6 days) and 6.4 days (5.1-7.9 days), respectively. When analysed separately, results for ACEi or ARB patient groups were similar for both death and discharge. CONCLUSIONS: In critically ill COVID-19 patients with comorbid hypertension, use of ACEi/ARBs prior to ICU admission was associated with a reduced risk of in-hospital mortality following adjustment for baseline characteristics although patients with ACEi/ARB showed longer length of hospital stay. Clinical trial registration The registration number: ACTRN12620000421932; The date of registration: 30, March 2020; The URL of the registration: https://www.australianclinicaltrials.gov.au/anzctr/trial/ACTRN12620000421932 .

Impact of inter-vendor variability on evaluation of left ventricular mechanical dispersion.

PURPOSE: Left ventricular mechanical dispersion (LVMD) is a novel speckle tracking parameter for prognostic assessment of arrhythmic risk prediction. There is growing evidence to support its use in a variety of cardiomyopathic processes. There is paucity of data addressing any presence of inter-vendor discrepancies for LVMD. The aim of this study was to assess inter-vendor variability of LVMD in vendor specific software (VSS) and vendor independent software (VIS) in subjects with preserved and reduced left ventricular function. METHODS: Fifty-nine subjects (14 normal subjects and 45 subjects with cardiac disease) were recruited and 2D speckle tracking echocardiographic images were acquired on two different ultrasound machines (GE and Philips). LVMD was measured by two different VSS (EchoPac GE and QLAB Philips) and one VIS (TomTec Arena). RESULTS: There was significant bias and wide limits of agreement (LOA) in the overall cohort observed between two different VSS (17.6 ms; LOA: -29.6 to 64.8; r: .47). There was acceptable bias and narrower LOA with good agreement for LVMD between images obtained on different vendors when performed on VIS (-3.1 ms; LOA: -27.6 to 21.4; r: .75). QLAB LVMD was consistently higher than GE LVMD and TomTec LVMD in both preserved and reduced left ventricular function. LVMD measurements have high intra-vendor reproducibility with excellent inter and intra-observer agreement. CONCLUSIONS: There was acceptable bias and narrower LOA for LVMD assessment on a VIS. Inter-vendor variability exists for LVMD assessment between VSS. Serial measurements of LVMD should be performed using a single vendor for consistent and reliable results.

Left atrial reservoir strain provides incremental value to left atrial volume index for evaluation of left ventricular filling pressure.

BACKGROUND: Left atrial analysis is employed in diastolic assessment with left atrial volume index (LAVI) incorporated in the 2016 ASE/EACVI diastology guideline algorithm. LAVI has sub-optimal correlation with invasive left ventricular filling pressure (LVFP) and incorporation of left atrial reservoir strain (LASr) may improve diastolic assessment. METHODS: A cross-sectional prospective study of 139 patients was undertaken with all patients undergoing transthoracic echocardiography immediately prior to cardiac catheterization with invasive evaluation of LVFP. LASr by speckle tracking echocardiography and conventional echocardiographic parameters were assessed in relation to invasive LVFP. Modification of the 2016 guideline algorithm was performed with incorporation of LASr in place of LAVI (LASr ≤23% indicating elevated LVFP). Accuracy of the modified and conventional algorithm were assessed for predicting invasive LVFP. RESULTS: The mean age was 63±12 years with 27% female. LASr demonstrated superior correlation and receiver operator characteristic for predicting LVFP than LAVI (LASr: r -.46 (p < 0.01), AUC: .82 vs LAVI: r .19 (p 0.02), AUC: .66). LASr of ≤23% was the optimal cut-off for discriminating elevated LVFP (sensitivity 80%, specificity 77%). Modification of the 2016 algorithm with incorporation of LASr in place of LAVI reclassified 12% of the patient cohort and improved concordance of echocardiographic and invasive LVFP assessment (modified algorithm κ .47 vs 2016 algorithm κ: .33). No patients were incorrectly reclassified by modified algorithm assessment. CONCLUSIONS: LASr better predicts invasive LVFP than LAVI. Modification of the 2016 guideline algorithm with incorporation of LASr in place of LAVI improves accuracy of echocardiographic assessment of LVFP.

Myocardial work and left ventricular contractile reserve during stress echocardiography: An angiographic validation.

OBJECTIVE: This study sought to determine the contractile reserve (CR) response to exercise stress echocardiography (ESE) quantified by the novel parameter, non-invasive myocardial work (MW), in subjects with angiographically proven coronary artery disease (CAD). METHODS: CR was measured by the relative change in ejection fraction (EF), global longitudinal strain (GLS) and MW indices from rest to peak exercise in 304 patients referred for clinically indicated ESE. Positive ESE patients proceeded to coronary angiography and further risk stratified based on either percutaneous or surgical intervention. RESULTS: CRGLS and global work index (CRGWI ) significantly decreased with exercise induced ischemia and angiographically proven significant CAD (CRGLS -1.6±3.5%; CRGWI -8.6±511 mm Hg% decrement, p < 0.001) compared to non-ischemic patients (CRGLS 1.4±2.2%; CRGWI 398±404 mm Hg% improvement). Global constructive work (CRGCW ) was significantly higher (p < 0.0001) in non-ischemic (818±457 mm Hg%) and blunted in ischemic patients (208±550 mm Hg%). CRGCW (AUC .81; 95%CI:.75-.86) demonstrated the most association for inducible ischemia followed by CRGLS (AUC .75; 95%CI:.69-.80), CRGWI (AUC .73, 95%CI:.67-.79) and CREF (AUC .71; 95%CI:.65-.77, p < 0.001). Subgroup analysis showed patients requiring surgical revascularization demonstrated a significantly lower CRGWE (-11.5±7.6%, p < 0.05) as a result of reduced CRGCW (281±573 mm Hg%, p < 0.05) and increased global wasted work (CRGWW , 289±151 mm Hg%, p = 0.09). CONCLUSION: Multivessel disease requiring surgical revascularization have the greatest reduction in CR. MW may potentially improve detection of ischemia and further risk stratification during ESE to maximize the benefits of revascularization.

Sacubitril/Valsartan in Adult Congenital Heart Disease Patients With Chronic Heart Failure - A Single Centre Case Series and Call for an International Registry.

BACKGROUND: An improvement in life expectancy in patients suffering from adult congenital heart disease (ACHD) has corresponded with a rise in heart failure incidence within this group. An area that has not been addressed in ACHD heart failure guidelines has been the use of combined inhibition of angiotensin receptor-neprolysin pathways. This case series sought to demonstrate tolerability and 6-month outcome measures of sacubitril/valsartan use in ACHD patients with a severely impaired systemic ventricle. METHODS: A prospective cohort analysis of ACHD patients between December 2016 and September 2017 with severe systemic ventricular systolic dysfunction, New York Heart Association (NYHA) class II-III symptoms and eligible for commencement on a sacubitril/valsartan regime was undertaken. RESULTS: Five (5) consecutive patients were included in this cohort review, 80% male, mean age 41.8 (±19) years and mean systemic ventricular ejection fraction 27% (±3.6%). Two (2) patients with pre-existing D-TGA and atrial baffle repair, one patient with Tetralogy of Fallot repair and pulmonary valve replacement (PVR), one patient with left atrial isomerism and partial atrioventricular (AV) canal defect repair and mitral valve replacement (MVR) and the last patient had biventricular repair for pulmonary atresia with MVR and PVR. Forty per cent (40%) of patients had a systemic right ventricle. All patients had NYHA functional class of ≥II, were on optimal tolerated doses ACE-I or ARB prior to sacubitril/valsartan combination. Six (6) months post commencement of sacubitril/valsartan patients experienced a mean improvement of one functional class. CONCLUSIONS: Our experience suggests that sacubitril/valsartan therapy is well tolerated in ACHD heart failure patients and is associated with improvement in functional class.

Comparison of 3D echocardiographic-derived indices using fully automatic left ventricular endocardial tracing (heart model) and semiautomatic tracing (3DQ-ADV).

AIMS: The availability of a true 3D dataset provides an opportunity for automation of left ventricular (LV) and left atrial (LA) measurements. Although manual and automated measurements of 3D volumes are known to correlate, the variance is an important parameter for the individual patient. The reasons for discrepancies remain unexplained. We hence aim to explain the disagreement between automated and manual LV and LA volumes. METHODS AND RESULTS: A total of 355 patients underwent standard clinical echo, with offline analysis in both fully- (Heart Model, Philips) and semiautomated (3DQ-Adv, Philips) assessment of routine indices of LV and LA function and shape. Each image was classified according to quality using a 4-point scale as well as the American Society for Echocardiography guidelines for appropriate use of contrast. Bland-Altman plots were used to assess agreement, and t tests were used to assess differences in agreement. Predictors of volume discrepancy were sought with linear regression. Measures of LV and LA volumes were greater with automatic than semiautomatic assessment. The difference in left ventricular end-diastolic volume was dependent on the number of regional wall-motion abnormalities (RWMA) (ß = 0.59, P < .04) and image quality (ß = 19.71, P = .02). RWMA predicted the difference in left ventricular end-systolic volume (ß = 0.83, P < .01) and left atrial end-systolic volume (ß = -1.01 P < .01). CONCLUSION: LV and LA volumes were higher with automatic than semiautomatic assessment. Image quality and RWMA may contribute to this discrepancy. These limitations need to be addressed before fully automatic assessment of 3D echocardiograms can be used in the clinic.

Pharmacokinetics of a novel dosing regimen of oral melatonin in critically ill patients.

BACKGROUND: Loss of circadian rhythms and reduced concentrations of endogenous melatonin are common in critically ill patients. After exogenous administration, supra-physiological concentrations in serum are only ephemeral, which may explain the absence of significant therapeutic effect on sleep. The aim of this study is to describe the pharmacokinetics of enteral melatonin in critically ill patients administered in a novel regimen aiming to simulate endogenous release. METHODS: Thirteen patients in the recovery phase of critical illness were randomised to receive enteral melatonin or placebo. In the melatonin group, a total of 6 mg was administered as solution through their feeding tube, commencing with a 3 mg loading dose at 9 pm and six subsequent 0.5 mg doses hourly. The placebo was administered using a similar regimen. Serial blood samples were taken and measured using a validated chromatographic method. The concentration-time data for serum melatonin concentrations were described using non-linear mixed-effects modelling. RESULTS: The observed concentrations in the melatonin patients were significantly higher than that observed in the placebo patients. The concentrations in the patients administered melatonin were also higher than endogenous melatonin concentrations previously reported in non-critically ill patients. The patients administered melatonin had a mean clearance, volume of distribution and absorption rate constant of melatonin was 55.2 L/h, 767 L and 0.76 h-1, respectively. CONCLUSIONS: Exogenous administration of melatonin with a loading dose of 3 mg followed by an hourly dose of 0.5 mg demonstrates good oral bioavailability and results in supra-physiological and sustained concentrations of serum melatonin during 12 h overnight.

The value of ultrasound enhancing agents in the echocardiographic acquisition of pulmonary artery systolic pressure: An invasive to non-invasive correlation study.

PURPOSE: Right heart catheterization (RHC) is the gold standard for the assessment of pulmonary artery systolic pressures (PASP). Despite high utilization of echocardiography for the non-invasive assessment of PASP, the data comparing real-time non-invasive echocardiographic PASP with invasive PASP is limited. Furthermore, evidence regarding the utility and diagnostic accuracy of ultrasound enhancing agents (UEA) for non-invasive PASP assessment is lacking. To evaluate the accuracy of non-invasive PASP assessment with real-time invasive measures and the incremental benefit of UEA in this setting. METHODS: This was a prospective cohort study of 90 patients, undergoing clinically indicated RHC for hemodynamic assessment. All patients underwent a limited echocardiogram during RHC. Tricuspid regurgitant velocity (TRV) was measured on unenhanced echo, in the setting of centrally administrated agitated saline, then as either centrally administered or peripherally administered UEA. RESULTS: Of the 90 patients enrolled in our study, 41% had pulmonary hypertension. The overall mean PASP measured by RHC was 32.8 mmHg (+/- 11.3 mmHg). Unenhanced echocardiograms had a moderate correlation with invasive PASP (r = 0.57; p = < 0.001) which improved to a strong correlation with administration of agitated saline (r = 0.75; p = < 0.001) or centrally administered UEA (r = 0.77; p = < 0.001), with the best correlation noted with peripherally administered UEA (r = 0.83; p = < 0.001). Against invasive PASP, agitated saline enhanced PASP had the lowest bias (0.12mmHg; -15.6 to 15.8mmHg) when compared with all other non-invasive measures of PASP. CONCLUSIONS: Unenhanced echocardiographic estimation of TRV was found to have a poorer correlation with invasively measured PASP when compared to agitated saline and centrally administered UEA. Agitated saline enhanced PASP demonstrated the lowest bias with invasive PASP when compared to other non-invasive measures of PASP.

The LATE score: A novel framework for echocardiographic evaluation of left ventricular filling pressure.

BACKGROUND: The LATE score (LATE: Left Atrial reservoir strain (LASr), Tricuspid regurgitation maximum velocity (TR Vmax), and E/e' average) is a novel framework for echocardiographic assessment of left ventricular filling pressure (LVFP). LATE = 0 indicates normal LVFP. LATE = 1 indicates resting LVFP is borderline elevated, and the patient may be at risk of pathological elevation of LVFP during exertion. LATE ≥2 indicates LVFP is severely elevated. METHODS: The LATE score was derived from reported thresholds of LASr and conventional echocardiographic parameters for predicting LVFP. The LATE score was prospectively evaluated in a cross-sectional study of 63 patients undergoing transthoracic echocardiography immediately prior to cardiac catheterization with invasive assessment of LVFP. Accuracy of the LATE score was compared to 2016 ASE diastology algorithms. RESULTS: Mean patient age was 62.9 ±â€¯13.6 years with 22% female. LATE = 0 in 29 patients, of which 24 (83%) had normal LVFP (mean LVFP 9 mmHg, SD ±3 mmHg). LATE = 1 in 23 patients, of which 11 (48%) had elevated LVFP (mean LVFP 12 mmHg, SD ±â€¯4 mmHg). LATE was ≥2 in 11 patients, all of which had elevated LVFP (100%) (mean LVFP 16 mmHg, SD ±3 mmHg). The LATE score showed greater agreement with invasive assessment than the 2016 algorithms (LATE kappa = 0.73, 2016 kappa = 0.37). CONCLUSIONS: The LATE score is a simple and effective tool for evaluation of LVFP that is more accurate than the 2016 algorithms. The LATE score provides insight beyond binary classification of normal versus elevated LVFP.

Novel echocardiographic pixel intensity quantification method for differentiating transthyretin cardiac amyloidosis from light chain cardiac amyloidosis and other phenocopies.

AIMS: Differentiating cardiac amyloidosis (CA) subtypes is important considering the significantly different therapies for transthyretin (ATTR)-CA and light chain (AL)-CA. Therefore, an echocardiographic method to distinguish ATTR-CA from AL-CA would provide significant value. We assessed a novel echocardiographic pixel intensity method to quantify myocardial calcification to differentiate ATTR-CA from phenocopies of CA and from AL-CA, specifically. METHODS AND RESULTS: 167 patients with ATTR-CA (n=53), AL-CA (n=32), hypertrophic cardiomyopathy (n=37), and advanced chronic kidney disease (n=45) were retrospectively evaluated. The septal reflectivity ratio (SRR) was measured as the average pixel intensity of the visible anterior septal wall divided by the average pixel intensity of the visible posterior lateral wall. SRR and other myocardial strain-based echocardiographic measures were evaluated with receiver operator characteristic analysis to evaluate accuracy in distinguishing ATTR-CA from AL-CA and other forms of left ventricular hypertrophy. Mean septal reflectivity ratio (SRR) was significantly higher in the ATTR-CA cohort compared to the other cohorts (p <0.001). SRR demonstrated the largest AUC (0.91, p<0.0001) for distinguishing ATTR from all other cohorts and specifically for distinguishing ATTR-CA from AL-CA (AUC=0.90, p<0.0001, specificity 96%, sensitivity 63%). There was excellent inter- and intra-operator reproducibility with an ICC of 0.91 (p <0.001) and 0.89 (p <0.001), respectively. CONCLUSION: The SRR is a reproducible and robust parameter for differentiating ATTR-CA from other phenocopies of CA and specifically ATTR-CA from AL-CA.

Macroscopic haematuria--a urological approach.

BACKGROUND: Haematuria is a common symptom with a multitude of differentials. It can often be a diagnostic dilemma. OBJECTIVE: This article looks at the role of the general practitioner in the investigation and initial management of macroscopic haematuria. DISCUSSION: Common urological causes of haematuria include urinary tract infection and ureteric and renal stones, but concurrent pathology should be suspected if haematuria is significant or persistent. Importantly, if benign conditions are excluded, and the haematuria continues, further investigation is advised, as this may be the only sign of an underlying genitourinary malignancy. Recommended investigations for haematuria include computed tomography intravenous pyelogram, urine cytology, urine microscopy and culture and blood tests (full blood examination, renal function and, in men, prostate-specific antigen). Patients with risk factors for genitourinary malignancy, macroscopic haematuria or those in whom no cause is found, should be referred to a urological service for further investigation including cystoscopy. Acute urinary retention is a common acute presentation of macroscopic haematuria. This can be managed with continuous irrigation and rarely requires emergency surgical intervention.

Circulating Cardiovascular Biomarkers in Cancer Therapeutics-Related Cardiotoxicity: Review of Critical Challenges, Solutions, and Future Directions.

Cardiotoxicity is a growing concern in the oncology population. Transthoracic echocardiography and multigated acquisition scans have been used for surveillance but are relatively insensitive and resource intensive. Innovative imaging techniques are constrained by cost and availability. More sensitive, cost-effective cardiotoxicity surveillance strategies are needed. Circulating cardiovascular biomarkers could provide a sensitive, low-cost solution. Biomarkers such as troponins, natriuretic peptides (NPs), novel upstream signals of oxidative stress, inflammation, and fibrosis as well as panomic technologies have shown substantial promise, and guidelines recommend baseline measurement of troponins and NPs in all patients receiving potential cardiotoxins. Nonetheless, supporting evidence has been hampered by several limitations. Previous reviews have provided valuable perspectives on biomarkers in cancer populations, but important analytic aspects remain to be examined in depth. This review provides comprehensive assessment of critical challenges and solutions in this field, with focus on analytical issues relating to biomarker measurement and interpretation. Examination of evidence pertaining to common and serious forms of cardiotoxicity reveals that improved study designs incorporating larger, more diverse populations, registry-based approaches, and refinement of current definitions are key. Further efforts to harmonize biomarker methodologies including centralized biobanking and analyses, novel decision limits, and head-to-head comparisons are needed. Multimarker algorithms incorporating machine learning may allow rapid, personalized risk assessment. These improvements will not only augment the predictive value of circulating biomarkers in cardiotoxicity but may elucidate both direct and indirect relationships between cardiovascular disease and cancer, allowing biomarkers a greater role in the development and success of novel anticancer therapies.

Exploration of the Utility of Speckle-Tracking Echocardiography During Mechanical Ventilation and Mechanical Circulatory Support.

This narrative review aims to discuss the potential applicability of speckle-tracking echocardiography (STE) in patients under mechanical ventilation (MV) and mechanical circulatory support (MCS). Both its benefits and limitations were considered through critical analyses of the current available evidence. DATA SOURCES AND STUDY SELECTION: A literature search was conducted in PubMed and Excerpta Medica Database indexed databases (2012-2021). In addition, the reference lists of all selected studies were manually scanned for further identification of potentially relevant studies. DATA EXTRACTION: The terms "Speckle-Tracking Echocardiography," "Mechanical Ventilation," "Mechanical Circulatory Support," "Extracorporeal Membrane Oxygenation," "Ventricular Assist Devices," and "Left Ventricular Unloading Devices" were searched for the identification of relevant articles for narrative synthesis. DATA SYNTHESIS: STE is a well-established post-processing method of analyzing myocardial function, with potentially greater clinical utility than conventional 2D echocardiography. STE has been incorporated into the guideline recommendations for both the diagnostic and prognostic evaluations of myocardial and valvular pathologies. However, the potential of STE application within critical care settings has not yet been fully realized. Its utility in the assessment of patients undergoing MV and MCS is substantial. Specifically, it may serve as an ideal modality in the assessment of subtle changes in cardiac function. In the limited number of studies reviewed, STE was consistently a more sensitive marker of myocardial functional change, compared with traditional markers of 2D and Doppler parameters during changes in MV and MCS. CONCLUSIONS: Although current evidence is extremely limited, STE strain is suggested to be a more sensitive and reproducible parameter of myocardial function than conventional echocardiographic parameters and may have value in the assessment of patients undergoing MV and MCS in critical care settings. Further studies in larger populations are required to elucidate STE's prognostic capability and its value as a point-of-care tool in guiding clinical practice for subjects under MV and MCS.

Global longitudinal strain as a prognostic marker in cardiac resynchronisation therapy: A systematic review.

PURPOSE: Cardiac resynchronisation therapy (CRT) has proven mortality benefits for heart failure patients with moderate to severe systolic left ventricular dysfunction and evidence of a left bundle branch block. Determining responders to this therapy can be difficult due to the presence of myocardial fibrosis and scar. Left ventricular global longitudinal strain (LV GLS) is a robust and sensitive measure of myocardial function and fibrosis that has significant prognostic value for a plethora of cardiac pathologies. Our aim was to perform a systematic review of the value of LV GLS for predicting outcomes in patients undergoing CRT. METHODS: A systematic review of the literature was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) protocol for reporting on systematic reviews and meta-analyses. An electronic search of all English, adult publications in EMBASE, MEDLINE/PubMed and the Cochrane Database of Systematic reviews was undertaken. RESULTS: The search yielded, 9 studies that included 3,981 patients with symptomatic heart failure, undergoing CRT implantation with LV GLS utilised as a predictor of all-cause mortality, cardiovascular death, rehospitalisation, LVAD implantation/ heart transplantation or left ventricular reverse remodelling. Significant heterogeneity was observed in study outcome measures, included populations, LV-GLS cut-offs and follow-up definitions, resulting in the inability to reliably conduct a meta-analyses. Overall, pre-CRT LV GLS was found to be a predictor of outcome post CRT insertion. CONCLUSIONS: In conclusion, all studies implied that incrementally abnormal baseline LV GLS pre-CRT implantation was associated with a long term poorer outcome.

Effect of Exogenous Melatonin Administration in Critically Ill Patients on Delirium and Sleep: A Randomized Controlled Trial.

INTRODUCTION: Sleep deprivation is a contributor for delirium in intensive care. Melatonin has been proposed as a pharmacological strategy to improve sleep, but studies have shown that the increase in plasma levels of melatonin do not correlate to a beneficial clinical effect; in addition, melatonin's short half-life may be a major limitation to achieving therapeutic levels. This study applies a previously published novel regimen of melatonin with proven sustained levels of melatonin during a 12 h period. In this study, the aim is to determine if such melatonin dosing positively influences on the sleep architecture and the incidence of delirium in intensive care. METHODS: Single center, randomized control trial with consecutive recruitment over 5 years. Medical and surgical patients were in a recovery phase, all weaning from mechanical ventilation. Randomized allocation to placebo or enteral melatonin, using a previously described regimen (loading dose of 3 mg at 21 h, followed by 0.5 mg hourly maintenance dose until 03am through a nasogastric tube). Sleep recordings were performed using polysomnogram at baseline (prior to intervention) and the third night on melatonin (postintervention recording). Delirium was assessed using the Richmond Agitation and the Confusion Assessment Method Scales. Environmental light and noise levels were recorded using a luxmeter and sound meter. RESULTS: 80 patients were screened, but 33 were recruited. Sleep studies showed no statistical differences on arousal index or length of sleep. Baseline delirium scores showed no difference between groups when compared to postintervention scores. RASS scores were 1 in both groups at baseline, compared to zero (drug group) and 0.5 (placebo group) posttreatment. CAM scores were zero (drug group) and 1 (placebo group) at baseline, compared to zero (in both groups) postintervention. CONCLUSION: High levels of plasma melatonin during the overnight period of intensive care cohort patients did not improve sleep nor decreased the prevalence of delirium. This trial is registered with Anzctr.org.au/ACTRN12620000661976.aspx.