De-escalation of antimicrobial therapy in ICU settings with high prevalence of multidrug-resistant bacteria: a multicentre prospective observational cohort study in patients with sepsis or septic shock.

BACKGROUND: De-escalation of empirical antimicrobial therapy, a key component of antibiotic stewardship, is considered difficult in ICUs with high rates of antimicrobial resistance. OBJECTIVES: To assess the feasibility and the impact of antimicrobial de-escalation in ICUs with high rates of antimicrobial resistance. METHODS: Multicentre, prospective, observational study in septic patients with documented infections. Patients in whom de-escalation was applied were compared with patients without de-escalation by the use of a propensity score matching by SOFA score on the day of de-escalation initiation. RESULTS: A total of 262 patients (mean age 62.2 ± 15.1 years) were included. Antibiotic-resistant pathogens comprised 62.9%, classified as MDR (12.5%), extensively drug-resistant (49%) and pandrug-resistant (1.2%). In 97 (37%) patients de-escalation was judged not feasible in view of the antibiotic susceptibility results. Of the remaining 165 patients, judged as patients with de-escalation possibility, de-escalation was applied in 60 (22.9%). These were matched to an equal number of patients without de-escalation. In this subset of 120 patients, de-escalation compared with no de-escalation was associated with lower all-cause 28 day mortality (13.3% versus 36.7%, OR 0.27, 95% CI 0.11-0.66, P = 0.006); ICU and hospital mortality were also lower. De-escalation was associated with a subsequent collateral decrease in the SOFA score. Cox multivariate regression analysis revealed de-escalation as a significant factor for 28 day survival (HR 0.31, 95% CI 0.14-0.70, P = 0.005). CONCLUSIONS: In ICUs with high levels of antimicrobial resistance, feasibility of antimicrobial de-escalation was limited because of the multi-resistant pathogens isolated. However, when de-escalation was feasible and applied, it was associated with lower mortality.

Limitation of Non-Beneficial Interventions and their Impact on the Intensive Care Unit Costs.

Introduction: Using a plan to limit non-beneficial life support interventions has significantly reduced harm and loss of dignity for patients at the end of life. The association of these limitations with patients' clinical characteristics and health care costs in the intensive care unit (ICU) needs further scientific evidence. Aim of the study: To explore decisions to limit non-beneficial life support interventions, their correlation with patients' clinical data, and their effect on the cost of care in the ICU. Material and Methods: We included all patients admitted to the general ICU of a hospital in Greece in a two-year (2019-2021) prospective study. Data collection included patient demographic and clinical variables, data related to decisions to limit (withholding, withdrawing) non-beneficial interventions (NBIs), and economic data. Comparisons were made between patients with and without limitation decisions. Results: NBIs were limited in 164 of 454 patients (36.12%). Patients with limitation decisions were associated with older age (70y vs. 62y; p<0,001), greater disease severity score (APACHE IV, 71 vs. 50; p<0,001), longer length of stay (7d vs. 4.5d; p<0,001), and worse prognosis of death (APACHE IV PDR, 48.9 vs. 17.35; p<0,001). All cost categories and total cost per patient were also higher than the patient without limitation of NBIs (9247,79€ vs. 8029,46€, p<0,004). The mean daily cost has not differed between the groups (831,24€ vs. 832,59€; p<0,716). However, in the group of patients with limitations, all cost categories, including the average daily cost (767.31€ vs. 649.12€) after the limitation of NBIs, were reduced to a statistically significant degree (p<0.001). Conclusions: Limiting NBIs in the ICU reduces healthcare costs and may lead to better management of ICU resource use.

Lopinavir/ritonavir as a third agent in the antiviral regimen for SARS-CoV-2 infection.

Corona Virus Disease (CoVID-19) is an emerging public health problem rapidly spread globally. New treatment options for patients with severe symptoms and ways of reducing transmission in the community are taken into consideration. A retrospective study was conducted in the Department of Infectious Diseases of Alexandroupolis (Greece) including 16 patients with CoVID-19. They were classified into two groups, A and B. Group A received lopinavir/ritonavir as a third agent in the antiviral regimen, while group B did not. Lymphocytes were more significantly increased in patients of group A. Ferritin serum levels were also decreased significantly in these patients. Number of days needed for a first negative result of Real Time- Polymerase Chain Reaction (RT-PCR) was lower for Group A. The present study suggests that lopinavir/ritonavir may reduce the viral carriage in a shorter period of time compared with other antiviral regimens. Further studies are needed in order to evaluate the effectiveness of lopinavir/ritonavir in the treatment of patients with SARS-CoV-2 infection.

Ultrasonographic assessment of diaphragmatic contraction and relaxation properties: correlations of diaphragmatic displacement with oesophageal and transdiaphragmatic pressure.

Transdiaphragmatic (Pdi) and oesophageal pressures (Pes) are useful in understanding the pathophysiology of the respiratory system. They provide insight into respiratory drive, intrinsic positive end-expiratory pressure, diaphragmatic fatigue and weaning failure. BACKGROUND: The use of Pdi and Pes in clinical practice is restricted due to the invasiveness of the technique and the cumbersome equipment needed. On the other hand, diaphragmatic displacement is non-invasively and easily assessed with M-mode ultrasound. PURPOSE: We observed striking similarities in shape and magnitude between M-mode diaphragmatic displacement, Pes and Pdi pressures. The study aimed to evaluate if the information provided by these two pressures could be obtained non-invasively from the diaphragmatic displacement curve. MATERIAL AND METHODS: In 14 consecutive intubated patients undergoing a weaning trial, simultaneous recordings of Pes and Pdi pressures and the diaphragmatic displacement were assessed while breathing spontaneously and during a sniff-like manoeuvre. Moreover, the slope of the diaphragmatic displacement curve during relaxation was compared with the maximal relaxation rate (MRR) obtained from the Pdi curve. RESULTS: More than 200 breaths were analysed in pairs. Diaphragmatic displacement significantly correlated with Pdi (R2=0.33, p<0.001) and Pes (R2=0.44, p<0.001), and this correlation further improved during sniff (R2=0.47, p<0.001) and (R2=0.64, p<0.001), respectively. Additionally, a significant correlation was found between the relaxation slope derived from the diaphragmatic displacement curve and the MRR derived from the Pdi curve, both in normal breathing (R2=0.379, p<0.001) and during the sniff manoeuvre (R2=0.71, p<0.001). CONCLUSIONS: M-mode diaphragmatic displacement parameters correlate well with the ones obtained from oesophageal pressure and Pdi, particularly during sniffing. Diaphragmatic displacement assessment possibly offers an alternative non-invasive solution for understanding and clinically monitoring the diaphragmatic contractile properties and weaning failure due to diaphragmatic fatigue.

Heart Rate Variability: A Potential Tool for Monitoring Immunomodulatory Effects of Parenteral Fish Oil Feeding in Patients With Sepsis.

Fish oil, rich in the very-long chain omega (ω)-3 polyunsaturated fatty acids (PUFAs), has been found to have immunomodulatory effects in different groups of critically ill patients. In addition, its parenteral administration seems to attenuate the inflammatory response within 2 to 3 days. The activation of the cholinergic anti-inflammatory pathway has been suggested to mediate such immunoregulatory effects. As different experimental studies have convincingly illustrated that enhanced vagal tone can decrease pro-inflammatory cytokine secretion, novel monitoring tools of its activity at the bedside could be developed, to evaluate nutritional manipulation of immune response in the critically ill. Heart rate variability (HRV) is the variability of R-R series in the electrocardiogram and could be a promising surrogate marker of immune response and its modulation during fish oil feeding, rich in ω-3 PUFAs. Heart rate variability is an indirect measure of autonomic nervous system (ANS) output, reflecting mainly fluctuations in ANS activity. Through HRV analysis, different "physiomarkers" can be estimated that could be used as early and more accurate "smart alarms" because they are based on high-frequency measurements and are much more easy to get at the bedside. On the contrary, various "biomarkers" such as cytokines exhibit marked interdependence, pleiotropy, and their plasma concentrations fluctuate from day to day in patients with sepsis. In this respect, an inverse relation between different HRV components and inflammatory biomarkers has been observed in patients with severe sepsis and septic shock, whereas a beneficial effect of ω-3 PUFAs on HRV has been demonstrated in patients with cardiovascular diseases. Consequently, in this article, we suggest that a beneficial effect of ω-3 PUFAs on HRV and clinical outcome in patients with sepsis merits further investigation and could be tested in future clinical trials as a real-time monitoring tool of nutritional manipulation of the inflammatory response in the critically ill.

Melatonin and cortisol exhibit different circadian rhythm profiles during septic shock depending on timing of onset: a prospective observational study.

BACKGROUND: Septic shock has been found to disrupt circadian rhythms. Moreover, timing of onset has been associated with different circadian profiles in experimental studies. RESULTS: In this prospective study, we enrolled 26 patients divided into two groups: Group A (N = 15) included subjects who had septic shock at the time of ICU admission and Group B (N = 11) included patients who developed septic shock during ICU admission. 6-Sulfatoxymelatonin (aMT6s) and cortisol levels were measured in urine samples every 4 h over a 24-h period. Two sets of samples were taken from Group A (entry/septic shock and exit) and three sets from Group B (entry, septic shock and exit). Mean, amplitude that is the difference between peak and mean values, as well as peak time, were estimated for both aMT6s and cortisol. In Group A, amplitude of aMT6s upon entry (septic shock) was reduced in relation to exit (437.2 ± 309.2 vs. 674.1 ± 657.6 ng/4 h, p < 0.05). Peak time occurred earlier (10:00 p.m. vs. 07:00 a.m, p < 0.05) and correlated with higher APACHE II score and longer ICU stay. In Group B, aMT6s mean values were significantly increased during septic shock (2492.2 ± 1709.1 ng/4 h) compared to both entry (895.4 ± 715.5 ng/4 h) and exit (1308.6 ± 1214.4 ng/4 h, p < 0.05 for all comparisons). Amplitude of aMT6s was also elevated during septic shock (794.8 ± 431.8 ng/4 h) in relation to entry (293.1 ± 275.9 ng/4 h, p < 0.05). Regarding cortisol rhythm in Group A, during septic shock amplitude was increased compared to exit (13.3 ± 31 ng/4 h vs. 8.7 ± 21.2 ng/4 h p < 0.05) and correlated with reduced hospital length of stay. In Group B, cortisol mean values and amplitude during septic shock (10 ± 5.3 and 3 ± 1.8 ng/4 h, respectively) were significantly reduced compared to both entry (30 ± 57.9 and 12.3 ± 27.3 ng/4 h) and exit (14.4 ± 20.7 and 6.6 ± 8.7 ng/4 h, p < 0.05 for all comparisons) and correlated with higher SOFA score and longer ICU and hospital stay. CONCLUSIONS: Septic shock induced inverse changes of aMT6s and cortisol circadian rhythm profiles both within and between different groups of patients, depending on timing of onset. Reduced rhythmicity was correlated with severity of disease and longer ICU stay.

Resting Energy Expenditure in Critically Ill Patients With Spontaneous Intracranial Hemorrhage.

BACKGROUND: Data on energy requirements of patients with spontaneous intracranial hemorrhage (SICH) are scarce. The objective of this study was to determine the resting energy expenditure (REE) in critically ill patients with SICH and to compare it with the predicted basal metabolic rate (BMR). METHODS: In 30 nonseptic patients with SICH, the REE was measured during the 10 first posthemorrhage days with the use of indirect calorimetry (IC). Predicted BMR was also evaluated by the Harris-Benedict (HB) equation. Bland-Altman analysis was used to evaluate the agreement between measured and predicted values. The possible effect of confounding factors (demographics, disease, and severity of illness score) on the evolution of continuous variables was also tested. RESULTS: mean predicted BMR, calculated by the HB equation, was 1580.3 ± 262 kcal/d, while measured REE was 1878.9 ± 478 kcal/d (117.5% BMR). Compared with BMR, measured REE values showed a statistically significant increase at all studied points (P < .005). Measured and predicted values showed a good correlation (r = 0.73, P < .001), but the test of agreement between the 2 methods with the Bland-Altman analysis showed a mean bias (294.6 ± 265.6 kcal/d) and limits of agreement (-226 to 815.29 kcal/d) that were beyond the clinically acceptable range. REE values presented a trend toward increase over time (P = .077), reaching significance (P < .005) after the seventh day. Significant correlation was found between REE and temperature (P = .002, r = 0.63), as well as between REE and cortisol level (P = .017, r = 0.62) on the 10th day. No correlation was identified between REE and depth of sedation, as well as Acute Physiology and Chronic Health Evaluation II, Glasgow Coma Scale, and Hunt and Hess scores. CONCLUSIONS: During the early posthemorrhagic stage, energy requirements of critically ill patients with SICH are increased, presenting a trend toward increase over time. Compared with IC, the HB equation underestimates energy requirements and is inefficient in detecting individual variability of REE in this group of patients.