126 research outputs found
Meta-analysis of hemodynamic optimization: relationship to methodological quality
INTRODUCTION: To review systematically the effect of interventions aimed at hemodynamic optimization and to relate this to the quality of individual published trials. METHODS: A systematic, computerized bibliographic search of published studies and citation reviews of relevant studies was performed. All randomized clinical trials in which adult patients were included in a trial deliberately aiming at an optimized or maximized hemodynamic condition of the patients (with oxygen delivery, cardiac index, oxygen consumption, mixed venous oxygen saturation and/or stroke volume as end-points) were selected. A total of 30 studies were selected for independent review. Two reviewers extracted data on population, intervention, outcome and methodological quality. Agreement between reviewers was high: differences were eventually resolved by third-party decision. The methodological quality of the studies was moderate (mean 9.0, SD 1.7), and the outcomes of the randomized clinical trials were not related to their quality. RESULTS: Efforts to achieve an optimized hemodynamic condition resulted in a decreased mortality rate (relative risk ratio (RR) 0.75 (95% confidence interval (CI) 0.62 to 0.90) in all studies combined. This was due to a significantly decreased mortality in peri-operative intervention studies (RR 0.66 (95% CI 0.54 to 0.81). Overall, patients with sepsis and overt organ failure do not benefit from this method (RR 0.92 (95% CI 0.75 to 1.11)). CONCLUSION: This systematic review showed that interventions aimed at hemodynamic optimization reduced mortality. In particular, trials including peri-operative interventions aimed at the hemodynamic optimization of high-risk surgical patients reduce mortality. Overall, this effect was not related to the trial quality
Gastrointestinal symptoms during the first week of intensive care are associated with poor outcome : a prospective multicentre study
The study aimed to develop a gastrointestinal (GI) dysfunction score predicting 28-day mortality for adult patients needing mechanical ventilation (MV).
377 adult patients from 40 ICUs with expected duration of MV for at least 6 h were prospectively studied. Predefined GI symptoms, intra-abdominal pressures (IAP), feeding details, organ dysfunction and treatment were documented on days 1, 2, 4 and 7.
The number of simultaneous GI symptoms was higher in nonsurvivors on each day. Absent bowel sounds and GI bleeding were the symptoms most significantly associated with mortality. None of the GI symptoms alone was an independent predictor of mortality, but gastrointestinal failure (GIF)-defined as three or more GI symptoms-on day 1 in ICU was independently associated with a threefold increased risk of mortality. During the first week in ICU, GIF occurred in 24 patients (6.4 %) and was associated with higher 28-day mortality (62.5 vs. 28.9 %, P = 0.001). Adding the created subscore for GI dysfunction (based on the number of GI symptoms) to SOFA score did not improve mortality prediction (day 1 AUROC 0.706 [95 % CI 0.647-0.766] versus 0.703 [95 % CI 0.643-0.762] in SOFA score alone).
An increasing number of GI symptoms independently predicts 28 day mortality with moderate accuracy. However, it was not possible to develop a GI dysfunction score, improving the performance of the SOFA score either due to data set limitations, definition problems, or possibly indicating that GI dysfunction is often secondary and not the primary cause of other organ failure
Citrulline supplementation improves organ perfusion and arginine availability under conditions with enhanced arginase activity
Enhanced arginase-induced arginine consumption is believed to play a key role in the pathogenesis of sickle cell disease-induced end organ failure. Enhancement of arginine availability with l-arginine supplementation exhibited less consistent results; however, l-citrulline, the precursor of l-arginine, may be a promising alternative. In this study, we determined the effects of l-citrulline compared to l-arginine supplementation on arginine-nitric oxide (NO) metabolism, arginine availability and microcirculation in a murine model with acutely-enhanced arginase activity. The effects were measured in six groups of mice (n = 8 each) injected intraperitoneally with sterile saline or arginase (1000 IE/mouse) with or without being separately injected with l-citrulline or l-arginine 1 h prior to assessment of the microcirculation with side stream dark-field (SDF)-imaging or in vivo NO-production with electron spin resonance (ESR) spectroscopy. Arginase injection caused a decrease in plasma and tissue arginine concentrations. l-arginine and l-citrulline supplementation both enhanced plasma and tissue arginine concentrations in arginase-injected mice. However, only the citrulline supplementation increased NO production and improved microcirculatory flow in arginase-injected mice. In conclusion, the present study provides for the first time in vivo experimental evidence that l-citrulline, and not l-arginine supplementation, improves the end organ microcirculation during conditions with acute arginase-induced arginine deficiency by increasing the NO concentration in tissues
Development of the Gastrointestinal Dysfunction Score (GIDS) for critically ill patients – A prospective multicenter observational study (iSOFA study)
Background & aims: To develop a five grade score (0–4 points) for the assessment of gastrointestinal (GI) dysfunction in adult critically ill patients. Methods: This prospective multicenter observational study enrolled consecutive adult patients admitted to 11 intensive care units in nine countries. At all sites, daily clinical data with emphasis on GI clinical symptoms were collected and intra-abdominal pressure measured. In five out of 11 sites, the biomarkers citrulline and intestinal fatty acid-binding protein (I-FABP) were measured additionally. Cox models with time-dependent scores were used to analyze associations with 28- and 90-day mortality. The models were estimated with stratification for study center. Results: We included 540 patients (224 with biomarker measurements) with median age of 65 years (range 18–94), the Simplified Acute Physiology Score II score of 38 (interquartile range 26–53) points, and Sequential Organ Failure Assessment (SOFA) score of 6 (interquartile range 3–9) points at admission. Median ICU length of stay was 3 (interquartile range 1–6) days and 90-day mortality 18.9%. A new five grade Gastrointestinal Dysfunction Score (GIDS) was developed based on the rationale of the previously developed Acute GI Injury (AGI) grading. Citrulline and I-FABP did not prove their potential for scoring of GI dysfunction in critically ill. GIDS was independently associated with 28- and 90-day mortality when added to SOFA total score (HR 1.40; 95%CI 1.07–1.84 and HR 1.40; 95%CI 1.02–1.79, respectively) or to a model containing all SOFA subscores (HR 1.48; 95%CI 1.13–1.92 and HR 1.47; 95%CI 1.15–1.87, respectively), improving predictive power of SOFA score in all analyses. Conclusions: The newly developed GIDS is additive to SOFA score in prediction of 28- and 90-day mortality. The clinical usefulness of this score should be validated prospectively. Trial registration: NCT02613000, retrospectively registered 24 November 2015.SCOPUS: ar.jinfo:eu-repo/semantics/publishe
The impact of regionalized trauma care on the distribution of severely injured patients in the Netherlands
BACKGROUND: Twenty years ago, an inclusive trauma system was implemented in the Netherlands. The goal of this study was to evaluate the impact of structured trauma care on the concentration of severely injured patients over time. METHODS: All severely injured patients (Injury Severity Score [ISS] ≥ 16) documented in the Dutch Trauma Registry (DTR) in the calendar period 2008–2018 were included for analysis. We compared severely injured patients, with and without severe neurotrauma, directly brought to trauma centers (TC) and non-trauma centers (NTC). The proportion of patients being directly transported to a trauma center was determined, as was the total Abbreviated Injury Score (AIS), and ISS. RESULTS: The documented number of severely injured patients increased from 2350 in 2008 to 4694 in 2018. During this period, on average, 70% of these patients were directly admitted to a TC (range 63–74%). Patients without severe neurotrauma had a lower chance of being brought to a TC compared to those with severe neurotrauma. Patients directly presented to a TC were more severely injured, reflected by a higher total AIS and ISS, than those directly transported to a NTC. CONCLUSION: Since the introduction of a well-organized trauma system in the Netherlands, trauma care has become progressively centralized, with more severely injured patients being directly presented to a TC. However, still 30% of these patients is initially brought to a NTC. Future research should focus on improving pre-hospital triage to facilitate swift transfer of the right patient to the right hospital
Evaluation of the Berlin polytrauma definition:A Dutch nationwide observational study
BACKGROUND The Berlin polytrauma definition (BPD) was established to identify multiple injury patients with a high risk of mortality. The definition includes injuries with an Abbreviated Injury Scale score of >= 3 in >= 2 body regions (2AIS >= 3) combined with the presence of >= 1 physiological risk factors (PRFs). The PRFs are based on age, Glasgow Coma Scale, hypotension, acidosis, and coagulopathy at specific cutoff values. This study evaluates and compares the BPD with two other multiple injury definitions used to identify patients with high resource utilization and mortality risk, using data from the Dutch National Trauma Register (DNTR). METHODS The evaluation was performed based on 2015 to 2018 DNTR data. First, patient characteristics for 2AIS >= 3, Injury Severity Score (ISS) of >= 16, and BPD patients were compared. Second, the PRFs prevalence and odds ratios of mortality for 2AIS >= 3 patients were compared with those from the Deutsche Gesellschaft fur Unfallchirurgie Trauma Register. Subsequently, the association between PRF and mortality was assessed for 2AIS >= 3-DNTR patients and compared with those with an ISS of >= 16. RESULTS The DNTR recorded 300,649 acute trauma admissions. A total of 15,711 patients sustained an ISS of >= 16, and 6,263 patients had suffered a 2AIS >= 3 injury. All individual PRFs were associated with a mortality of >30% in 2AIS >= 3-DNTR patients. The increase in PRFs was associated with a significant increase in mortality for both 2AIS >= 3 and ISS >= 16 patients. A total of 4,264 patients met the BPDs criteria. Overall mortality (27.2%), intensive care unit admission (71.2%), and length of stay were the highest for the BPD group. CONCLUSION This study confirms that the BPD identifies high-risk patients in a population-based registry. The addition of PRFs to the anatomical injury scores improves the identification of severely injured patients with a high risk of mortality. Compared with the ISS >= 16 and 2AIS >= 3 multiple injury definitions, the BPD showed to improve the accuracy of capturing patients with a high medical resource need and mortality rate
Early enteral nutrition in critically ill patients: ESICM clinical practice guidelines.
To provide evidence-based guidelines for early enteral nutrition (EEN) during critical illness.
We aimed to compare EEN vs. early parenteral nutrition (PN) and vs. delayed EN. We defined "early" EN as EN started within 48 h independent of type or amount. We listed, a priori, conditions in which EN is often delayed, and performed systematic reviews in 24 such subtopics. If sufficient evidence was available, we performed meta-analyses; if not, we qualitatively summarized the evidence and based our recommendations on expert opinion. We used the GRADE approach for guideline development. The final recommendations were compiled via Delphi rounds.
We formulated 17 recommendations favouring initiation of EEN and seven recommendations favouring delaying EN. We performed five meta-analyses: in unselected critically ill patients, and specifically in traumatic brain injury, severe acute pancreatitis, gastrointestinal (GI) surgery and abdominal trauma. EEN reduced infectious complications in unselected critically ill patients, in patients with severe acute pancreatitis, and after GI surgery. We did not detect any evidence of superiority for early PN or delayed EN over EEN. All recommendations are weak because of the low quality of evidence, with several based only on expert opinion.
We suggest using EEN in the majority of critically ill under certain precautions. In the absence of evidence, we suggest delaying EN in critically ill patients with uncontrolled shock, uncontrolled hypoxaemia and acidosis, uncontrolled upper GI bleeding, gastric aspirate >500 ml/6 h, bowel ischaemia, bowel obstruction, abdominal compartment syndrome, and high-output fistula without distal feeding access
The impact of the Trauma Triage App on pre-hospital trauma triage: design and protocol of the stepped-wedge, cluster-randomized TESLA trial
Abstract Background Field triage of trauma patients is crucial to get the right patient to the right hospital within a particular time frame. Minimization of undertriage, overtriage, and interhospital transfer rates could substantially reduce mortality rates, life-long disabilities, and costs. Identification of patients in need of specialized trauma care is predominantly based on the judgment of Emergency Medical Services professionals and a pre-hospital triage protocol. The Trauma Triage App is a smartphone application that includes a prediction model to aid Emergency Medical Services professionals in the identification of patients in need of specialized trauma care. The aim of this trial is to assess the impact of this new digital approach to field triage on the primary endpoint undertriage. Methods The Trauma triage using Supervised Learning Algorithms (TESLA) trial is a stepped-wedge cluster-randomized controlled trial with eight clusters defined as Emergency Medical Services regions. These clusters are an integral part of five inclusive trauma regions. Injured patients, evaluated on-scene by an Emergency Medical Services professional, suspected of moderate to severe injuries, will be assessed for eligibility. This unidirectional crossover trial will start with a baseline period in which the default pre-hospital triage protocol is used, after which all clusters gradually implement the Trauma Triage App as an add-on to the existing triage protocol. The primary endpoint is undertriage on patient and cluster level and is defined as the transportation of a severely injured patient (Injury Severity Score ≥ 16) to a lower-level trauma center. Secondary endpoints include overtriage, hospital resource use, and a cost-utility analysis. Discussion The TESLA trial will assess the impact of the Trauma Triage App in clinical practice. This novel approach to field triage will give new and previously undiscovered insights into several isolated components of the diagnostic strategy to get the right trauma patient to the right hospital. The stepped-wedge design allows for within and between cluster comparisons. Trial registration Netherlands Trial Register, NTR7243. Registered 30 May 2018, https://www.trialregister.nl/trial/7038
Citrulline a More Suitable Substrate than Arginine to Restore NO Production and the Microcirculation during Endotoxemia
BACKGROUND: Impaired microcirculation during endotoxemia correlates with a disturbed arginine-nitric oxide (NO) metabolism and is associated with deteriorating organ function. Improving the organ perfusion in endotoxemia, as often seen in patients with severe infection or systemic inflammatory response syndrome (SIRS) is, therefore, an important therapeutic target. We hypothesized that supplementation of the arginine precursor citrulline rather than arginine would specifically increase eNOS-induced intracellular NO production and thereby improve the microcirculation during endotoxemia. METHODOLOGY/PRINCIPAL FINDINGS: To study the effects of L-Citrulline and L-Arginine supplementation on jejunal microcirculation, intracellular arginine availability and NO production in a non-lethal prolonged endotoxemia model in mice. C57/Bl6 mice received an 18 hrs intravenous infusion of endotoxin (LPS, 0.4 µg • g bodyweight(-1) • h(-1)), combined with either L-Citrulline (6.25 mg • h-1), L-Arginine (6.25 mg • h(-1)), or L-Alanine (isonitrogenous control; 12.5 mg • h(-1)) during the last 6 hrs. The control group received an 18 hrs sterile saline infusion combined with L-Alanine or L-Citrulline during the last 6 hrs. The microcirculation was evaluated at the end of the infusion period using sidestream dark-field imaging of jejunal villi. Plasma and jejunal tissue amino-acid concentrations were measured by HPLC, NO tissue concentrations by electron-spin resonance spectroscopy and NOS protein concentrations using Western blot. CONCLUSION/SIGNIFICANCE: L-Citrulline supplementation during endotoxemia positively influenced the intestinal microvascular perfusion compared to L-Arginine-supplemented and control endotoxemic mice. L-Citrulline supplementation increased plasma and tissue concentrations of arginine and citrulline, and restored intracellular NO production in the intestine. L-Arginine supplementation did not increase the intracellular arginine availability. Jejunal tissues in the L-Citrulline-supplemented group showed, compared to the endotoxemic and L-Arginine-supplemented endotoxemic group, an increase in degree of phosphorylation of eNOS (Ser 1177) and a decrease in iNOS protein level. In conclusion, L-Citrulline supplementation during endotoxemia and not L-Arginine reduced intestinal microcirculatory dysfunction and increased intracellular NO production, likely via increased intracellular citrulline and arginine availability
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