Purpose
The optimal target blood glucose concentration for acute glycemic control remains unclear because few studies have directly compared 144–180 with 110–144 or >180 mg/dL. Accordingly, we ...performed a network meta-analysis to compare four different target blood glucose levels (<110, 110–144, 144–180, and >180 mg/dL) in terms of the benefit and risk of insulin therapy.
Methods
We included all of the studies from three systematic reviews and searched the PubMed and Cochrane databases for other studies investigating glucose targets among critically ill patients. The primary outcome was hospital mortality, and the secondary outcomes were sepsis or bloodstream infection and the risk of hypoglycemia. Network meta-analysis to identify an optimal target glucose concentration.
Results
The network meta-analysis included 18,098 patients from 35 studies. There were no significant differences in the risk of mortality and infection among the four blood glucose ranges overall or in subgroup analysis. Conversely, target concentrations of <110 and 110–144 mg/dL were associated with a four to ninefold increase in the risk of hypoglycemia compared with 144–180 and >180 mg/dL. However, there were no significant differences between the target concentrations of 144–180 and >180 mg/dL.
Conclusions
This network meta-analysis found no significant difference in the risk of mortality and infection among four target blood glucose ranges in critically ill patients, but indicated that target blood glucose levels of <110 and 110–144 mg/dL were associated with a higher risk of hypoglycemia than target levels of 144–180 and >180 mg/dL. Further studies are required to refute or confirm our findings.
Expanding elderly populations are a major social challenge in advanced countries worldwide and have led to a rapid increase in the number of elderly patients in intensive care units (ICUs). ...Innovative advances in medical technology have enabled lifesaving of patients in ICUs, but there remain various problems to improve their long‐term prognoses. Post‐intensive care syndrome (PICS) refers to physical, cognition, and mental impairments that occur during ICU stay, after ICU discharge or hospital discharge, as well as the long‐term prognosis of ICU patients. Its concept also applies to pediatric patients (PICS‐p) and the mental status of their family (PICS‐F). Intensive care unit‐acquired weakness, a syndrome characterized by acute symmetrical limb muscle weakness after ICU admission, belongs to physical impairments in three domains of PICS. Prevention of PICS requires performance of the ABCDEFGH bundle, which incorporates the prevention of delirium, early rehabilitation, family intervention, and follow‐up from the time of ICU admission to the time of discharge. Diary, nutrition, nursing care, and environmental management for healing are also important in the prevention of PICS. This review outlines the pathophysiology, prevention, and future directions of PICS.
Conceptual framework of post‐intensive care syndrome (PICS). ICU, intensive care unit; PICS‐F, PICS – family.
Glucose control to prevent both hyperglycemia and hypoglycemia is important in an intensive care unit. Arterial blood gas analyzers and glucose meters are commonly used to measure blood-glucose ...concentration in an intensive care unit; however, their accuracies are still unclear.
We performed a systematic literature search (January 1, 2001, to August 31, 2012) to find clinical studies comparing blood-glucose values measured with glucose meters and/or arterial blood gas analyzers with those simultaneously measured with a central laboratory machine in critically ill adult patients.
We reviewed 879 articles and found 21 studies in which the accuracy of blood-glucose monitoring by arterial blood gas analyzers and/or glucometers by using central laboratory methods as references was assessed in critically ill adult patients. Of those 21 studies, 11 studies in which International Organization for Standardization criteria, error-grid method, or percentage of values within 20% of the error of a reference were used were selected for evaluation. The accuracy of blood-glucose measurements by arterial blood gas analyzers and glucose meters by using arterial blood was significantly higher than that of measurements with glucose meters by using capillary blood (odds ratios for error: 0.04, P<0.001; and 0.36, P<0.001). The accuracy of blood-glucose measurements with arterial blood gas analyzers tended to be higher than that of measurements with glucose meters by using arterial blood (P=0.20). In the hypoglycemic range (defined as <81 mg/dl), the incidence of errors using these devices was higher than that in the nonhypoglycemic range (odds ratios for error: arterial blood gas analyzers, 1.86, P=0.15; glucose meters with capillary blood, 1.84, P=0.03; glucose meters with arterial blood, 2.33, P=0.02). Unstable hemodynamics (edema and use of a vasopressor) and use of insulin were associated with increased error of blood glucose monitoring with glucose meters.
Our literature review showed that the accuracy of blood-glucose measurements with arterial blood gas analyzers was significantly higher than that of measurements with glucose meters by using capillary blood and tended to be higher than that of measurements with glucose meters by using arterial blood. These results should be interpreted with caution because of the large variation of accuracy among devices. Because blood-glucose monitoring was less accurate within or near the hypoglycemic range, especially in patients with unstable hemodynamics or receiving insulin infusion, we should be aware that current blood glucose-monitoring technology has not reached a high enough degree of accuracy and reliability to lead to appropriate glucose control in critically ill patients.
Circulating lipopolysaccharide (LPS) concentrations are often elevated in patients with sepsis or various endogenous diseases related to bacterial translocation from the gut. Systemic inflammatory ...responses induced by endotoxemia induce severe involuntary loss of skeletal muscle, termed muscle wasting, which adversely affects the survival and functional outcomes of these patients. Currently, no drugs are available for the treatment of endotoxemia-induced skeletal muscle wasting. Here, we tested the effects of TAK-242, a Toll-like receptor 4 (TLR4)-specific signalling inhibitor, on myotube atrophy in vitro and muscle wasting in vivo induced by endotoxin. LPS treatment of murine C2C12 myotubes induced an inflammatory response (increased nuclear factor-κB activity and interleukin-6 and tumour necrosis factor-α expression) and activated the ubiquitin-proteasome and autophagy proteolytic pathways (increased atrogin-1/MAFbx, MuRF1, and LC-II expression), resulting in myotube atrophy. In mice, LPS injection increased the same inflammatory and proteolytic pathways in skeletal muscle and induced atrophy, resulting in reduced grip strength. Notably, pretreatment of cells or mice with TAK-242 reduced or reversed all the detrimental effects of LPS in vitro and in vivo. Collectively, our results indicate that pharmacological inhibition of TLR4 signalling may be a novel therapeutic intervention for endotoxemia-induced muscle wasting.
To assess the knowledge and use of the Assessment, prevention, and management of pain; spontaneous awakening and breathing trials; Choice of analgesia and sedation; Delirium assessment; Early ...mobility and exercise; and Family engagement and empowerment (ABCDEF) bundle to implement the Pain, Agitation, Delirium guidelines.
Worldwide online survey.
Intensive care.
A cross-sectional online survey using the Delphi method was administered to intensivists worldwide, to assess the knowledge and use of all aspects of the ABCDEF bundle.
There were 1,521 respondents from 47 countries, 57% had implemented the ABCDEF bundle, with varying degrees of compliance across continents. Most of the respondents (83%) used a scale to evaluate pain. Spontaneous awakening trials and spontaneous breathing trials are performed in 66% and 67% of the responder ICUs, respectively. Sedation scale was used in 89% of ICUs. Delirium monitoring was implemented in 70% of ICUs, but only 42% used a validated delirium tool. Likewise, early mobilization was "prescribed" by most, but 69% had no mobility team and 79% used no formal mobility scale. Only 36% of the respondents assessed ICU-acquired weakness. Family members were actively involved in 67% of ICUs; however, only 33% used dedicated staff to support families and only 35% reported that their unit was open 24 hr/d for family visits.
The current implementation of the ABCDEF bundle varies across individual components and regions. We identified specific targets for quality improvement and adoption of the ABCDEF bundle. Our data reflect a significant but incomplete shift toward patient- and family-centered ICU care in accordance with the Pain, Agitation, Delirium guidelines.
Preclinical animal studies precede the majority of clinical trials. While the clinical definitions of sepsis and recommended treatments are regularly updated, a systematic review of preclinical ...models of sepsis has not been done and clear modeling guidelines are lacking. To address this deficit, a Wiggers-Bernard Conference on preclinical sepsis modeling was held in Vienna in May, 2017. The goal of the conference was to identify limitations of preclinical sepsis models and to propose a set of guidelines, defined as the "Minimum Quality Threshold in Preclinical Sepsis Studies" (MQTiPSS), to enhance translational value of these models. A total of 31 experts from 13 countries participated and were divided into six thematic Working Groups: Study Design, Humane modeling, Infection types, Organ failure/dysfunction, Fluid resuscitation, and Antimicrobial therapy endpoints. As basis for the MQTiPSS discussions, the participants conducted a literature review of the 260 most highly cited scientific articles on sepsis models (2002-2013). Overall, the participants reached consensus on 29 points; 20 at "recommendation" and nine at "consideration" strength. This Executive Summary provides a synopsis of the MQTiPSS consensus. We believe that these recommendations and considerations will serve to bring a level of standardization to preclinical models of sepsis and ultimately improve translation of preclinical findings. These guideline points are proposed as "best practices" for animal models of sepsis that should be implemented. To encourage its wide dissemination, this article is freely accessible on the Intensive Care Medicine Experimental and Infection journal websites. In order to encourage its wide dissemination, this article is freely accessible in Shock, Infection, and Intensive Care Medicine Experimental.
There is increasing recognition that a major pathophysiologic event in sepsis is the progression to an immunosuppressive state in which the host is unable to eradicate invading pathogens. Although ...there are likely numerous causes for the immunosuppression, expression of negative costimulatory molecules on immune effector cells is a likely contributing factor. PD-1 is a recently described, negative costimulatory molecule that has potent effects to inhibit T cell activation, cytokine production, and cytotoxic functions. PD-1 plays a critical role in the host response to specific pathogens, but relatively little work has been done on the possible effects of PD-1 in sepsis. We hypothesized that the anti-PD-1 antibody would improve survival in sepsis. Mice underwent CLP, and PD-1 expression was quantitated. Additionally, the effects of anti-PD-1 antibody on lymphocyte apoptosis, cytokine production, host immunity, and survival were determined. PD-1 expression increased beginning 48 h after sepsis, and >20% of CD4 and CD8 T cells were positive by 7 days. Anti-PD-1 antibody administered 24 h after sepsis prevented sepsis-induced depletion of lymphocytes and DCs, increased Bcl-xL, blocked apoptosis, and improved survival. Anti-PD-1 also prevented the loss in DTH, a key indicator of immunocompetence in sepsis. Thus, delayed administration of anti-PD-1 antibody, an important therapeutic advantage, was effective in sepsis. Furthermore, these results add to the growing body of evidence that modulation of the positive and negative costimulatory pathways on immune cells represents a viable therapeutic approach in reversing immunosuppression and improving sepsis survival.
This study aimed to determine the accuracy of the quick Sequential Organ Failure Assessment (qSOFA) score in predicting mortality among prehospital patients with and without infection. This ...single-center, retrospective, cross-sectional study was conducted among patients who arrived via the emergency medical services (EMS). We calculated the qSOFA score and Modified Early Warning Score (MEWS) from prehospital records. We identified patients as infected if they received intravenous antibiotics at the emergency department or within the first 24 hours. Receiver operating characteristic analysis was used to evaluate and compare the performance of the qSOFA score, each physiological parameter, and the MEWS in predicting admission and in-hospital mortality in patients with and without infection. Multivariate analysis was used to evaluate the qSOFA score and other risk factors. Out of 1574 prehospital patients, 47.1% were admitted and 3.2% died in the hospital. The performance of the qSOFA score in predicting in-hospital mortality in noninfected patients was 0.70, higher than for each parameter and the MEWS. The areas under the curve for the qSOFA+ model vs. the qSOFA- model was 0.77 vs. 0.68 for noninfected patients (p <0.05) and 0.71 vs. 0.68 for infected patients (p = 0.41). The likelihood ratio test comparing the qSOFA- and qSOFA+ groups demonstrated significant improvement for noninfected patients (p <0.01). Multivariate regression analysis for in-hospital mortality demonstrated that the qSOFA score is an independent prognosticator for in-hospital mortality, especially among noninfected patients (odds ratio, 3.60; p <0.01). In conclusion, the prehospital qSOFA score was associated with in-hospital mortality in noninfected patients and may be a beneficial tool for identifying deteriorating patients in the prehospital setting.
This systematic review and meta-analysis of randomized clinical trials aimed to investigate the efficacy of early mobilization among critically ill adult patients.
We searched CENTRAL, MEDLINE, and ...Igaku-Chuo-Zasshi (a Japanese bibliographic database) databases until April 2019 and included randomized control trials to compare early mobilization started within 1 week of intensive care unit (ICU) admission and earlier-than-usual care with the usual care or mobilization initiated later than the intervention. Two authors independently extracted the data of the included studies and assessed their quality. The primary outcomes were in-hospital mortality, length of ICU/hospital stay, and health-related quality of life (QOL).
Among 1085 titles/abstracts screened, 11 studies (including 1322 patients) were included in the meta-analysis, which was conducted using the random-effects model. The pooled relative risk for in-hospital mortality comparing early mobilization to usual care (control) was 1.12 (95% CI confidence interval: 0.80 to 1.58,
= 0%). The pooled mean differences for duration of ICU and hospital stay were -1.54 (95% CI: -3.33 to 0.25,
= 90%) and -2.86 (95% CI: -5.51 to -0.21,
= 85%), respectively. The pooled mean differences at 6 months post-discharge, as measured by the Short Form 36-Item Health Survey and Euro-QOL EQ-5D, were 4.65 (95% CI: -16.13 to 25.43,
= 86%) for physical functioning and 0.29 (95% CI: -11.19 to 11.78,
= 66%) for the visual analog scale.
Our study indicated no apparent differences between early mobilization and usual care in terms of in-hospital mortality and health-related QOL. Detailed larger studies are warranted to evaluate the impact of early mobilization on in-hospital mortality and health-related QOL in critically ill patients.
PROSPERO (identifier CRD42019139265).
PDF
