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Purpose: To quantify potential heterogeneity of treatment effect (HTE), of early sedation with dexmedetomidine (DEX) compared with usual care, and identify patients who have a high probability of lower or higher 90-day mortality according to age, and other identified clusters., Methods: Bayesian analysis of 3904 critically ill adult patients expected to receive invasive ventilation > 24 h and enrolled in a multinational randomized controlled trial comparing early DEX with usual care sedation., Results: HTE was assessed according to age and clusters (based on 12 baseline characteristics) using a Bayesian hierarchical models. DEX was associated with lower 90-day mortality compared to usual care in patients > 65 years (odds ratio [OR], 0.83 [95% credible interval [CrI] 0.68-1.00], with 97.7% probability of reduced mortality across broad categories of illness severity. Conversely, the probability of increased mortality in patients ≤ 65 years was 98.5% (OR 1.26 [95% CrI 1.02-1.56]. Two clusters were identified: cluster 1 (976 patients) mostly operative, and cluster 2 (2346 patients), predominantly non-operative. There was a greater probability of benefit with DEX in cluster 1 (OR 0.86 [95% CrI 0.65-1.14]) across broad categories of age, with 86.4% probability that DEX is more beneficial in cluster 1 than cluster 2., Conclusion: In critically ill mechanically ventilated patients, early sedation with dexmedetomidine exhibited a high probability of reduced 90-day mortality in older patients regardless of operative or non-operative cluster status. Conversely, a high probability of increased 90-day mortality was observed in younger patients of non-operative status. Further studies are needed to confirm these findings.

Background: Dexmedetomidine produces sedation while maintaining a degree of arousability and may reduce the duration of mechanical ventilation and delirium among patients in the intensive care unit (ICU). The use of dexmedetomidine as the sole or primary sedative agent in patients undergoing mechanical ventilation has not been extensively studied., Methods: In an open-label, randomized trial, we enrolled critically ill adults who had been undergoing ventilation for less than 12 hours in the ICU and were expected to continue to receive ventilatory support for longer than the next calendar day to receive dexmedetomidine as the sole or primary sedative or to receive usual care (propofol, midazolam, or other sedatives). The target range of sedation-scores on the Richmond Agitation and Sedation Scale (which is scored from -5 [unresponsive] to +4 [combative]) was -2 to +1 (lightly sedated to restless). The primary outcome was the rate of death from any cause at 90 days., Results: We enrolled 4000 patients at a median interval of 4.6 hours between eligibility and randomization. In a modified intention-to-treat analysis involving 3904 patients, the primary outcome event occurred in 566 of 1948 (29.1%) in the dexmedetomidine group and in 569 of 1956 (29.1%) in the usual-care group (adjusted risk difference, 0.0 percentage points; 95% confidence interval, -2.9 to 2.8). An ancillary finding was that to achieve the prescribed level of sedation, patients in the dexmedetomidine group received supplemental propofol (64% of patients), midazolam (3%), or both (7%) during the first 2 days after randomization; in the usual-care group, these drugs were administered as primary sedatives in 60%, 12%, and 20% of the patients, respectively. Bradycardia and hypotension were more common in the dexmedetomidine group., Conclusions: Among patients undergoing mechanical ventilation in the ICU, those who received early dexmedetomidine for sedation had a rate of death at 90 days similar to that in the usual-care group and required supplemental sedatives to achieve the prescribed level of sedation. More adverse events were reported in the dexmedetomidine group than in the usual-care group. (Funded by the National Health and Medical Research Council of Australia and others; SPICE III ClinicalTrials.gov number, NCT01728558.)., (Copyright © 2019 Massachusetts Medical Society.)

Background: Continuous-wave Doppler (CWD) ultrasound through the left ventricular outflow tract is one modality used for non-invasive cardiac output measurement. The ultrasonic cardiac output monitor (USCOM) is a relatively new monitor which uses a small, transcutaneous ultrasound probe to measure cardiac output with CWD via the suprasternal window. It is faster and less complex to train new users than conventional echocardiography. In addition to stroke volume (SV), the USCOM can calculate stroke volume variation (SVV) and the Smith-Madigan inotropy index (SMII), which is an estimate of the pre-load independent contractility of the myocardium., Objective: To assess the level of agreement between cardiac output measured with conventional echocardiography and with USCOM., Methods: A prospective, observational, multicentre trial of patients admitted to the intensive care units of two hospitals. After excluding patients with aortic stenosis, any patient undergoing a clinically indicated echocardiogram also underwent a subsequent USCOM study for comparison., Results: We enrolled 121 patients in the study, with aortic stenosis the main reason for patient exclusion. Of the study patients, 63% were mechanically ventilated, 84% were in sinus rhythm, and the mean age of the study cohort was 66 years (SD, 17 years). There was a very strong correlation between SV as measured by the USCOM and by echocardiography. The mean difference in SV was 0.33 mL (SD, 5.62 mL), r 2 = 0.956, and Bland-Altman analysis confirmed no significant bias with acceptable limits of agreement between the methods. Patients who were fluid responsive had an SVV cut point on the receiver operating characteristic curve of 21%, and sensitivity and specificity of 95%. A low SMII (< 1.1 watts/m 2 ) calculated with the USCOM did not correlate well with low cardiac output status, with a sensitivity of only 69%., Conclusions: SV (and thus cardiac output) measured using the USCOM correlated well with echocardiographic cardiac output measurement, which suggests that the USCOM could be a valuable haemodynamic tool for assessment of cardiac output and fluid responsiveness in critically ill patients if patients with aortic stenosis are excluded. Inotropy, as a parameter of low cardiac output, was not useful in this cohort of patients.

Objective: To assess the feasibility and safety of delivering early goal-directed sedation compared with standard sedation., Design: Pilot prospective, multicenter, randomized, controlled trial., Setting: Six ICUs., Patients: Critically ill adults mechanically ventilated for greater than 24 hours., Interventions: Patients randomized to early goal-directed sedation received a dexmedetomidine-based algorithm targeted to light sedation (Richmond Agitation Sedation Score of -2 to 1). Patients randomized to standard sedation received propofol and/or midazolam-based sedation as clinically appropriate., Measurements and Main Results: The main feasibility outcomes were time to randomization and proportion of Richmond Agitation Sedation Score assessments in the first 48 hours in the light and deep sedation range. Safety outcomes were delirium-free days, vasopressor and physical restraints use, and device removal. Randomization occurred within a median (interquartile range) of 1.1 hours (0.46-1.9) after intubation or ICU admission for out of ICU intubation. Patients in the early goal-directed sedation (n = 21) mean (SD) Acute Physiology and Chronic Health Evaluation II score was 20.2 (6.2) versus 18.6 (8.8; p = 0.53) in the standard sedation (n = 16). A significantly higher proportion of patients was lightly sedated on days 1, 2, and 3 (12/19 [63.2%], 19/21 [90.5%], and 18/20 [90%] vs 2/14 [14.3%], 8/15 [53.3%], and 9/15 [60%]; p = 0.005, 0.011, 0.036) and more Richmond Agitation Sedation Scale assessments between (-2 and 1), in the first 48 hours (203/307 [66%] versus (74/197 [38%]; p = 0.01) in the early goal-directed sedation versus standard sedation, respectively. Early goal-directed sedation patients received midazolam on 6 of 173 (3.5%) versus 4 of 114 (3.5%) standard sedation patient-days when dexmedetomidine was given. Propofol was given to 16 of 21 (76%) of early goal-directed sedation versus 16 of 16 (100%) of standard sedation patients (p = 0.04). Early goal-directed sedation patients had 101 of 175 (58%) versus 54 of 114 (47%; p = 0.27) delirium-free days and required significantly less physical restraints 1 (5%) versus 5 (31%; p = 0.03) than standard sedation patients. There were no differences in vasopressor use and self-extubation., Conclusions: Delivery of early goal-directed sedation was feasible, appeared safe, achieved early light sedation, minimized benzodiazepines and propofol, and decreased the need for physical restraints. The findings of this pilot study justify further investigation of early goal-directed sedation.

Rationale: Choice and intensity of early (first 48 h) sedation may affect short- and long-term outcome., Objectives: To investigate the relationships between early sedation and time to extubation, delirium, and hospital and 180-day mortality among ventilated critically ill patients in the intensive care unit (ICU)., Methods: Multicenter (25 Australia and New Zealand hospitals) prospective longitudinal (ICU admission to 28 d) cohort study of medical/surgical patients ventilated and sedated 24 hours or more. We assessed administration of sedative agents, ventilation time, sedation depth using Richmond Agitation Sedation Scale (RASS, four hourly), delirium (daily), and hospital and 180-day mortality. We used multivariable Cox regression to quantify relationships between early deep sedation (RASS, -3 to -5) and patients' outcomes., Measurements and Main Results: We studied 251 patients (mean age, 61.7 ± 15.9 yr; mean Acute Physiology and Chronic Health Evaluation [APACHE] II score, 20.8 ± 7.8), with 21.1% (53) hospital and 25.8% (64) 180-day mortality. Over 2,678 study days, we completed 14,736 RASS assessments. Deep sedation occurred in 191 (76.1%) patients within 4 hours of commencing ventilation and in 171 (68%) patients at 48 hours. Delirium occurred in 111 (50.7%) patients with median (interquartile range) duration of 2 (1-4) days. After adjusting for diagnosis, age, sex, APACHE II, operative, elective, hospital type, early use of vasopressors, and dialysis, early deep sedation was an independent predictor of time to extubation (hazard ratio [HR], 0.90; 95% confidence interval [CI], 0.87-0.94; P < 0.001), hospital death (HR, 1.11; 95% CI, 1.02-1.20; P = 0.01), and 180-day mortality (HR, 1.08; 95% CI, 1.01-1.16; P = 0.026) but not delirium occurring after 48 hours (P = 0.19)., Conclusions: Early sedation depth independently predicts delayed extubation and increased mortality, making it a potential target for interventional studies.

The year 2009 was characterized by a pandemic with a new virus, the 2009 H1N1 influenza virus. This pandemic was responsible for thousands of deaths worldwide, many more hospital admissions, and thousands of admissions to intensive care units (ICUs). Among those admitted to ICUs, the pandemic was associated with a mortality of approximately 16%, a high incidence of acute lung injury and, in some cases, acute respiratory distress syndrome severe enough to require support with extracorporeal membrane oxygenation. As part of such a critical illness, a percentage of patients developed acute kidney injury (AKI) which complicated their clinical course and, in some patients, required support by renal replacement therapy. In a case series from Mexico, the incidence of severe AKI was reported in about 30% of the patients. Similarly, at the Austin Hospital, of 13 cases, 8 developed AKI with 3 being classified in the failure category of the RIFLE classification. Among the patients with AKI, hospital mortality was approximately 25%. Of the AKI patients, 3 (37.5%) received renal replacement therapy and, among these, 1 died. In a case of severe AKI and multi-organ failure from whom histological material was obtained, the renal histopathological findings were typical of acute tubular necrosis. One patient who suffered from hypoxic brain injury due to cardiac arrest at home secondary to H1N1 pneumonia became a kidney and liver donor. There was no evidence of viral infiltration on kidney biopsy and the recipient did not develop H1N1 infection., (2010 S. Karger AG, Basel.)

The authors reflect on the pregnancy risks of women in 21st century. The authors mention that pregnant women need to have high standard medical care against any infectious diseases like influenza A/H1N1. They state that maternal mortality rates (MMR) in high-income countries like Australia are lower compared with low-income countries like the sub-Saharan African countries. They adds that pregnant women with respiratory illnesses like pneumonia need to be admitted into intensive case unit.