Clinical efficacy of hydroxychloroquine in patients with covid-19 pneumonia who require oxygen: observational comparative study using routine care data.

This article by Mahevas and others was first published in the BMJ online during May 2020.
Objective:  To assess the effectiveness of hydroxychloroquine in patients admitted to hospital with coronavirus disease 2019 (covid-19) pneumonia who require oxygen.
Design:  Comparative observational study using data collected from routine care.
Setting:  Four French tertiary care centres providing care to patients with covid-19 pneumonia between 12 March and 31 March 2020.
Participants:  181 patients aged 18-80 years with documented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia who required oxygen but not intensive care.
Interventions:  Hydroxychloroquine at a dose of 600 mg/day within 48 hours of admission to hospital (treatment group) versus standard care without hydroxychloroquine (control group).
Main Outcome Measures:  The primary outcome was survival without transfer to the intensive care unit at day 21. Secondary outcomes were overall survival, survival without acute respiratory distress syndrome, weaning from oxygen, and discharge from hospital to home or rehabilitation (all at day 21). Analyses were adjusted for confounding factors by inverse probability of treatment weighting.
Results:  In the main analysis, 84 patients who received hydroxychloroquine within 48 hours of admission to hospital (treatment group) were compared with 89 patients who did not receive hydroxychloroquine (control group). Eight additional patients received hydroxychloroquine more than 48 hours after admission. In the weighted analyses, the survival rate without transfer to the intensive care unit at day 21 was 76% in the treatment group and 75% in the control group (weighted hazard ratio 0.9, 95% confidence interval 0.4 to 2.1). Overall survival at day 21 was 89% in the treatment group and 91% in the control group (1.2, 0.4 to 3.3). Survival without acute respiratory distress syndrome at day 21 was 69% in the treatment group compared with 74% in the control group (1.3, 0.7 to 2.6). At day 21, 82% of patients in the treatment group had been weaned from oxygen compared with 76% in the control group (weighted risk ratio 1.1, 95% confidence interval 0.9 to 1.3). Eight patients in the treatment group (10%) experienced electrocardiographic modifications that required discontinuation of treatment.
Conclusions:  Hydroxychloroquine has received worldwide attention as a potential treatment for covid-19 because of positive results from small studies. However, the results of this study do not support its use in patients admitted to hospital with covid-19 who require oxygen.
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Right ventricular dysfunction in neurologically deceased organ donors: An observational study in a tertiary-care organ donor referral centre

This research by Frenette and other was published online during 2019 in the Journal of Critical Care.
Purpose:  Right ventricular RV dysfunction among transplant recipients correlates with transplant outcome, but its frequency in donors is unknown. The purpose of this study was to describe the epidemiology of RV dysfunction in potential heart donors.”
Methods:  In a seven-year retrospective study of potential heart donors, we explored the incidence of RV dysfunction as observed on echocardiography and explored the association of four distinct factors with RV dysfunction: brain injury diagnosis, thoracic trauma, vasopressin infusion and left ventricular (LV) dysfunction.
Results:  All 123 potential heart donors underwent echocardiography: 55 had RV dysfunction (44.7%). Fourty-one (33.3%) had LV dysfunction. Isolated RV dysfunction was present in 27 subjects (22%). LV dysfunction was the only factor significantly associated with RV dysfunction (OR = 4.6 (95% CI 1.9–11.4)). We observed no difference in heart acceptance between subjects with or without RV dysfunction.
Conclusion:  We observed a high frequency of RV dysfunction in a sample of potential heart donors. However, the temporal evolution of RV dysfunction, the hemodynamic predictors of RV dysfunction, as well the link between donor RV dysfunction and recipient outcomes need to be assessed with further prospective studies.
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Impact of timing to source control in patients with septic shock: A prospective multi-center observational study

This work by Kim and others was first published on line during June 2019 in the Journal of Critical Care.
Purpose:  Current guidelines recommend that rapid source control should be adopted in patients not >6–12 h after sepsis is diagnosed. However, evidence level of this guideline is not specified, and there is no previous study on patients with septic shock visiting the emergency department (ED). Therefore, we aimed to assess the impact of rapid source control in patients with septic shock visiting the ED.
Materials and methods:  In a prospective, observational, multicenter, registry-based study in 11 EDs, Cox proportional hazards model was used to assess the independent effect of source control and time to source control on 28-day mortality.
Results:  Cox proportional hazard models revealed that 28-day mortality was significantly lower in patients who underwent source control (HR 0.538 (0.389–0.744), p < .001). However, no significant association between the performance of source control after 6 h or 12 h from enrollment and 28-day mortality was noted.
Conclusions:  Patients with septic shock visiting the ED who underwent source control showed better outcomes than those who did not. We failed to demonstrate the performance of rapid source control reduced the 28-day mortality in septic shock patients. Further studies are required to determine the impact of rapid source control in sepsis and septic shock.
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Effects of short-term hyperoxia on sytemic hemodynamics, oxygen transport, and microcirculation: An observational study in patients with septic shock and healthy volunteers

This research by Espinoza and others was published in Journal of Critical Care online in June 2019.
Purpose:  To characterize the microvascular effects of a brief period of hyperoxia, in patients with septic shock and in healthy volunteers.
Materials and methods:  In 20 patients with septic shock, we assessed systemic hemodynamics, sublingual microcirculation by SDF-videomicroscopy, and skin perfusion by capillary refill time (CRT), central-peripheral temperature (ΔT°), and perfusion index. Measurements were performed at baseline and after 5 min of inspired oxygen fraction of 1.00. Additionally, we studied 8 healthy volunteers, in whom hyperoxia was prolonged to 30 min.
Results:  In septic patients, hyperoxia increased mean arterial pressure and systemic vascular resistance, but cardiac output remained unchanged. The only significant change in sublingual microcirculation was a decreased heterogeneity flow index (1.03 [1.01–1.07] vs 1.01 [0.34–1.05], P = .002). Perfused vascular density (13.1 [12.0–15.0] vs 14.0 [12.2–14.8] mm/mm2, P = .21) and the other sublingual microvascular variables were unmodified. CRT and ΔT° did not change but perfusion index slightly decreased. In healthy volunteers, sublingual microcirculation and skin perfusion were stable.
Conclusions:  Short-term hyperoxia induced systemic cardiovascular changes but was not associated with noticeable derangement in sublingual microcirculation and skin perfusion. Nevertheless, longer exposures to hyperoxia might have produced different results.
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Early target attainment of continuous infusion piperacillin/tazobactam and meropenem in critically ill patients: A prospective observational study

This article by Hay and others was published on line in the Journal of Critical Care during April 2019.
Purpose:  To evaluate target attainment of empirically dosed continuous infusion piperacillin/tazobactam (TZP) and meropenem (MER) in critically ill patients.
Patients and methods:  Patients were sampled on a daily basis. TZP or MER concentrations were evaluated during the first two days antibiotic therapy. The lower limit of the target range was defined as unbound concentrations equaling 4 times the epidemiological cutoff value of P. aeruginosa. The upper limit of the target range was based on the risk of toxicity, i.e. unbound concentrations >160 mg/L for TZP and > 45 mg/L for MER. Multivariable logistic regression was used to evaluate factors associated with target attainment.
Results:  Data from 253 patients were analyzed. Overall, 76/205 (37.1%) and 36/48 (75%) of the patients receiving TZP or MER respectively, attained target concentrations. In multivariable analysis, estimated creatinine clearance was identified as a risk factor for target non-attainment (OR 0.988, 95%CI [0.982;0.994]). Patients receiving MER were more likely to attain target concentrations compared with patients receiving TZP (OR 6.02, 95%CI [2.12;18.4]).
Conclusion:  Target attainment of empiric antibiotic therapy in critically ill patients was low (37%) for TZP and moderate (75%) for MER, despite the use of a loading dose and despite optimization of the mode of infusion.
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Serum albumin as a risk factor for death in patients with prolonged sepsis: An observational study

This paper by Takegawa and colleagues was published on line in February 2019 in the Journal of Critical Care.
Purpose:  The aim of this study was to evaluate an association between nutritional biomarkers and prognosis in septic patients.
Methods:  We retrospectively searched the association between nutritional biomarkers including serum albumin (Alb), total protein (TP), total cholesterol (T-chol), and cholinesterase (ChE), and prognosis for septic patients treated in the ICU for >7 days. We used time-dependent Cox proportional hazard regression analysis to resolve the difference of the statistical weight of each day’s data for all 14 consecutive days among individual sepsis patients. The covariates were based on the minimum moving values determined from 1 day, 3 days, 7 days, and 14 days of serial data. The values of these covariates and ICU survival were considered as outcomes.
Results:  We included 136 septic patients. The decreases in the values of Alb, TP, T-chol, and ChE were significantly associated with the risk of death in the septic patients (p < .05). Especially, the daily changes of Alb were significantly associated with mortality during the ICU stay (p < .05).
Conclusions:  We found that the changes in serial data of the nutritional markers of Alb, TP, T-chol, and ChE reflected the higher risk of death in patients with prolonged sepsis.
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Noise in the intensive care unit and its influence on sleep quality: a multicenter observational study in Dutch intensive care units

This article by Simons and colleagues was published in the Critical Care October 2018 issue.
Background:  High noise levels in the intensive care unit (ICU) are a well-known problem. Little is known about the effect of noise on sleep quality in ICU patients. The study aim is to determine the effect of noise on subjective sleep quality.
Methods:  This was a multi-centre observational study in six Dutch ICUs. Noise recording equipment was installed in 2-4 rooms per ICU. Adult patients were eligible for the study 48 h after ICU admission and were followed up to maximum of five nights in the ICU. Exclusion criteria were presence of delirium and/or inability to be assessed for sleep quality. Sleep was evaluated using the Richards Campbell Sleep Questionnaire (range 0-100 mm). Noise recordings were used for analysis of various auditory parameters, including the number and duration of restorative periods. Hierarchical mixed model regression analysis was used to determine associations between noise and sleep.
Results:  In total, 64 patients (68% male), mean age 63.9 (± 11.7) years and mean Acute Physiology and Chronic Health Evaluation (APACHE) II score 21.1 (± 7.1) were included. Average sleep quality score was 56 ± 24 mm. The mean of the 24-h average sound pressure levels (LAeq, 24h) was 54.0 dBA (± 2.4). Mixed-effects regression analyses showed that background noise (β = - 0.51, p < 0.05) had a negative impact on sleep quality, whereas number of restorative periods (β = 0.53, p < 0.01) and female sex (β = 1.25, p < 0.01) were weakly but significantly correlated with sleep.
Conclusions:  Noise levels are negatively associated and restorative periods and female gender are positively associated with subjective sleep quality in ICU patients.
The full text of the article is available via this link.

Modes of mechanical ventilation vary between hospitals and intensive care units within a university healthcare system: a retrospective observational study

This research by Jabaley et al was published in the July 2018 issue of BMC Research Notes.
Objective:  As evidence-based guidance to aid clinicians with mechanical ventilation mode selection is scant, we sought to characterize the epidemiology thereof within a university healthcare system and hypothesized that nonconforming approaches could be readily identified. We conducted an exploratory retrospective observational database study of routinely recorded mechanical ventilation parameters between January 1, 2010 and December 31, 2016 from 12 intensive care units. Mode epoch count proportions were examined using Chi squared and Fisher exact tests as appropriate on an inter-unit basis with outlier detection for two test cases via post hoc pairwise analyses of a binomial regression model.  Results:  Final analysis included 559,734 mode epoch values. Significant heterogeneity was demonstrated between individual units (P < 0.05 for all comparisons). One unit demonstrated heightened utilization of high-frequency oscillatory ventilation, and three units demonstrated frequent synchronized intermittent mandatory ventilation utilization. Assist control ventilation was the most commonly recorded mode (51%), followed by adaptive support ventilation (23.1%). Volume-controlled modes were about twice as common as pressure-controlled modes (64.4% versus 35.6%). Our methodology provides a means by which to characterize the epidemiology of mechanical ventilation approaches and identify nonconforming practices. The observed variability warrants further clinical study about contributors and the impact on relevant outcomes.

The full text of this article in BMC Research Notes is available via this link.

Allostasis and sedation practices in intensive care evaluation: an observational pilot study.

This article by Moore and colleagues appeared in the June 2018 issue of Intensive Care Medicine Experimental.
Background:  A dysregulated stress response has been implicated in the pathogenesis of critical illness. Sedative agents utilised in the critically unwell patient may impact upon the stress response with a downstream negative effect on multiple organ systems. This study was designed to assess the feasibility of investigating components of the stress response as a sub-study of the current SPICE-III study (NCT01728558).
Methods:  This pilot observational cohort study was conducted in a single intensive care unit in Queensland, Australia. Enrolled patients were over 18 years who had been commenced on mechanical ventilation requiring sedation for less than 12h but expected to remain ventilated for > 24h. Blood samples were taken at 12h intervals over a 5-day period commencing at the time of enrolment, and subsequently tested for various markers of key efferent limbs of the stress axis.
Results:  The 12 patients recruited closely mirrored the population within the pilot study used to design SPICE-III. Eighty-nine percent (107/120) of all planned blood samples were obtained and drawn within 0h (0-0.3) of the planned sampling time point. Time from eligibility to enrolment was a median (IQR) 1.4h (0.36-9.19), and time from eligibility to the first blood sample was 4.79h (2.0-10.61). Physiological, hormonal, metabolic and cardiac biomarkers were consistent with an elevated stress response at baseline which mostly normalised over the 5-day study period. Plasma noradrenaline levels correlated with the dose of norepinephrine used.
Conclusions:  A larger sub-study of the SPICE-III study is feasible. The study has demonstrated a predictable trend of variation of the components of the blood panel during the evolution of critical illness and supports multiple sampling time points for the follow-up study.
The full text of the article is available via the link to “Download PDF” on this page.

Fluid therapy and outcome: a prospective observational study in 65 German intensive care units between 2010 and 2011

This article written by Ertmer et al was published in Annals of Intensive Care in the February 2018 edition.
Background:  Outcome data on fluid therapy in critically ill patients from randomised controlled trials may be different from data obtained by observational studies under “real-life” conditions. We conducted this prospective, observational study to investigate current practice of fluid therapy (crystalloids and colloids) and associated outcomes in 65 German intensive care units (ICUs). In total, 4545 adult patients who underwent intravenous fluid therapy were included. The main outcome measures were 90-day mortality, ICU mortality and acute kidney injury (AKI). Data were analysed using logistic and Cox regression models, as appropriate.
Results:  In the predominantly post-operative overall cohort, unadjusted 90-day mortality was 20.1%. Patients who also received colloids (54.6%) had a higher median Simplified Acute Physiology Score II [25 (interquartile range 11; 41) vs. 17 (7; 31)] and incidence of severe sepsis (10.2 vs. 7.4%) on admission compared to patients who received exclusively crystalloids (45.4%). 6% hydroxyethyl starch (HES 130/0.4) was the most common colloid (57.0%). Crude rates of 90-day mortality were higher for patients who received colloids (OR 1.845 [1.560; 2.181]). After adjustment for baseline variables, the HR was 1.666 [1.405; 1.976] and further decreased to indicate no associated risk (HR 1.003 [0.980; 1.027]) when it was adjusted for vasopressor use, severity of disease and transfusions. Similarly, the crude risk of AKI was higher in the colloid group (crude OR 3.056 [2.528; 3.694]), after adjustment for baseline variables OR 1.941 [1.573; 2.397], and after full adjustment OR 0.696 [0.629; 0.770]), the risk of AKI turned out to be reduced. The same was true for the subgroup of patients treated with 6% HES 130/0.4 (crude OR 1.931 [1.541; 2.419], adjusted for baseline variables OR 2.260 [1.730; 2.953] and fully adjusted OR 0.800 [0.704; 0.910]) as compared to crystalloids only.
Conclusions:  The present analysis of mostly post-operative patients in routine clinical care did not reveal an independent negative effect of colloids (mostly 6% HES 130/0.4) on renal function or survival after multivariable adjustment. Signals towards a reduced risk in subgroup analyses deserve further study.
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