Definition of infection after fracture fixation: A systematic review of randomized controlled trials to evaluate current practice.

INTRODUCTION: One of the most challenging musculoskeletal complications in modern trauma surgery is infection after fracture fixation (IAFF). Although infections are clinically obvious in many cases, a clear definition of the term IAFF is crucial, not only for the evaluation of published research data but also for the establishment of uniform treatment concepts. The aim of this systematic review was to identify the definitions used in the scientific literature to describe infectious complications after internal fixation of fractures. The hypothesis of this study was that the majority of fracture-related literature do not define IAFF. MATERIAL AND METHODS: A comprehensive search was performed in Embase, Cochrane, Google Scholar, Medline (OvidSP), PubMed publisher and Web-of-Science for randomized controlled trials (RCTs) on fracture fixation. Data were collected on the definition of infectious complications after fracture fixation used in each study. Study selection was accomplished through two phases. During the first phase, titles and abstracts were reviewed for relevance, and the full texts of relevant articles were obtained. During the second phase, full-text articles were reviewed. All definitions were literally extracted and collected in a database. Then, a classification was designed to rate the quality of the description of IAFF. RESULTS: A total of 100 RCT's were identified in the search. Of 100 studies, only two (2%) cited a validated definition to describe IAFF. In 28 (28%) RCTs, the authors used a self-designed definition. In the other 70 RCTs, (70%) there was no description of a definition in the Methods section, although all of the articles described infections as an outcome parameter in the Results section. CONCLUSION: This systematic review shows that IAFF is not defined in a large majority of the fracture-related literature. To our knowledge, this is the first study conducted with the objective to explore this important issue. The lack of a consensus definition remains a problem in current orthopedic trauma research and treatment and this void should be addressed in the near future.

An observational near-infrared spectroscopy study on cerebral autoregulation in post-cardiac arrest patients: time to drop 'one-size-fits-all' hemodynamic targets?

AIMS: A subgroup of patients with ROSC after cardiac arrest (CA) with disturbed cerebral autoregulation might benefit from higher mean arterial pressures (MAP). We aimed to (1) phenotype patients with disturbed autoregulation, (2) investigate whether these patients have a worse prognosis, (3) define an individual optimal MAP per patient and (4) investigate whether time under this individual optimal MAP is associated with outcome. METHODS: Prospective observational study in 51 post-CA patients monitored with near infrared spectroscopy. RESULTS: (1) 18/51 patients (35%) had disturbed autoregulation. Phenotypically, a higher proportion of patients with disturbed autoregulation had pre-CA hypertension (31±47 vs. 65±49%, p=0.02) suggesting that right shifting of autoregulation is caused by chronic adaptation of cerebral blood flow to higher blood pressures. (2) In multivariate analysis, patients with preserved autoregulation (n=33, 65%) had a significant higher 180-days survival rate (OR 4.62, 95% CI [1.06:20.06], p=0.04]. Based on an index of autoregulation (COX), the average COX-predicted optimal MAP was 85 mmHg in patients with preserved and 100 mmHg in patients with disturbed autoregulation. (3) An individual optimal MAP could be determined in 33/51 patients. (4) The time under the individual optimal MAP was negatively associated with survival (OR 0.97, 95% CI [0.96:0.99], p=0.02). The time under previously proposed fixed targets (65, 70, 75, 80 mmHg) was not associated with a differential survival rate. CONCLUSION: Cerebral autoregulation showed to be disturbed in 35% of post-CA patients of which a majority had pre-CA hypertension. Disturbed cerebral autoregulation within the first 24h after CA is associated with a worse outcome. In contrast to uniform MAP goals, the time spent under a patient tailored optimal MAP, based on an index of autoregulation, was negatively associated with survival.

Hemodynamic targets during therapeutic hypothermia after cardiac arrest: A prospective observational study.

AIM: In analogy with sepsis, current post-cardiac arrest (CA) guidelines recommend to target mean arterial pressure (MAP) above 65 mmHg and SVO2 above 70%. This is unsupported by mortality or cerebral perfusion data. The aim of this study was to explore the associations between MAP, SVO2, cerebral oxygenation and survival. METHODS: Prospective, observational study during therapeutic hypothermia (24h - 33 °C) in 82 post-CA patients monitored with near-infrared spectroscopy. RESULTS: Forty-three patients (52%) survived in CPC 1-2 until 180 days post-CA. The mean MAP range associated with maximal survival was 76-86 mmHg (OR 2.63, 95%CI [1.01; 6.88], p = 0.04). The mean SVO2 range associated with maximal survival was 67-72% (OR 8.23, 95%CI [2.07; 32.68], p = 0.001). In two separate multivariate models, a mean MAP (OR 3.72, 95% CI [1.11; 12.50], p=0.03) and a mean SVO2 (OR 10.32, 95% CI [2.03; 52.60], p = 0.001) in the optimal range persisted as independently associated with increased survival. Based on more than 1625000 data points, we found a strong linear relation between SVO2 (range 40-90%) and average cerebral saturation (R(2) 0.86) and between MAP and average cerebral saturation for MAP's between 45 and 101 mmHg (R(2) 0.83). Based on our hemodynamic model, the MAP and SVO2 ranges associated with optimal cerebral oxygenation were determined to be 87-101 mmHg and 70-75%. CONCLUSION: we showed that a MAP range between 76-86 mmHg and SVO2 range between 67% and 72% were associated with maximal survival. Optimal cerebral saturation was achieved with a MAP between 87-101 mmHg and a SVO2 between 70% and 75%. Prospective interventional studies are needed to investigate whether forcing MAP and SVO2 in the suggested range with additional pharmacological support would improve outcome.

Low hemoglobin levels are associated with lower cerebral saturations and poor outcome after cardiac arrest.

PURPOSE: Post-cardiac arrest (CA) patients have a large cerebral penumbra at risk for secondary ischemic damage in case of suboptimal brain oxygenation during ICU stay. The aims of this study were to investigate the association between hemoglobin, cerebral oxygenation (SctO2) and outcome in post-CA patients. METHODS: Prospective observational study in 82 post-CA patients. Hemoglobin, a corresponding SctO2 measured by NIRS and SVO2 in patients with a pulmonary artery catheter (n=62) were determined hourly during hypothermia in the first 24h of ICU stay. RESULTS: We found a strong linear relationship between hemoglobin and mean SctO2 (SctO2=0.70×hemoglobin+56 (R(2) 0.84, p=10(-6))). Hemoglobin levels below 10g/dl generally resulted in lower brain oxygenation. There was a significant association between good neurological outcome (43/82 patients in CPC 1-2 at 180 days post-CA) and admission hemoglobin above 13g/dl (OR 2.76, 95% CI 1.09:7.00, p=0.03) or mean hemoglobin above 12.3g/dl (OR 2.88, 95%CI 1.02:8.16, p=0.04). This association was entirely driven by results obtained in patients with a mean SVO2 below 70% (OR 6.25, 95%CI 1.33:29.43, p=0.01) and a mean SctO2 below 62.5% (OR 5.87, 95%CI 1.08:32.00, p=0.03). CONCLUSION: Hemoglobin levels below 10g/dl generally resulted in lower cerebral oxygenation. Average hemoglobin levels below 12.3g/dl were associated with worse outcome in patients with suboptimal SVO2 or SctO2. The safety of a universal restrictive transfusion threshold of 7g/dl can be questioned in post-CA patients.

Accuracy of continuous thermodilution cardiac output monitoring by pulmonary artery catheter during therapeutic hypothermia in post-cardiac arrest patients.

PURPOSE: Thermodilution continuous cardiac output measurements (TDCCO) by pulmonary artery catheter (PAC) have not been validated during therapeutic hypothermia in post-cardiac arrest patients. The calculated cardiac output based on the indirect Fick principle (FCO) using pulmonary artery blood gas mixed venous oxygen saturation (FCO-BG-SvO2) is considered as the gold standard. Continuous SvO2 by PAC (PAC-SvO2) has also not been validated previously during hypothermia. The aims of this study were (1) to compare FCO-BG-SvO2 with TDCCO, (2) to compare PAC-SvO2 with BG-SvO2 and finally (3) to compare FCO with SvO2 obtained via PAC or blood gas. METHODS: We analyzed 102 paired TDCCO/FCO-BG-SvO2 and 88 paired BG-SvO2/PAC-SvO2 measurements in 32 post-cardiac arrest patients during therapeutic hypothermia. RESULTS: TDCCO was significantly although poorly correlated with FCO-BG-SvO2 (R2 0.21, p<0.01) without systematic bias (-0.15±1.76 l/min). Analysis according to Bland and Altman however showed broad limits of agreement ([-3.61; 3.45] l/min) and an unacceptable high percentage error (105%). None of the criteria for clinical interchangeability were met. Concordance analysis showed that TDCCO had limited trending ability (R2 0.03). FCO based on PAC-SvO2 was highly correlated with FCO-BG-SvO2 (R2 0.72) with a small bias (-0.08±0.72 l/min) and slightly too high percentage error (44%). CONCLUSION: Our results show an extreme inaccuracy of TDCCO by PAC in post-cardiac arrest patients during therapeutic hypothermia. We found a reasonable correlation between BG-SvO2 and PAC-SvO2 and subsequently between FCO calculated with SvO2 obtained either via blood gas or PAC. The decision to start or titrate inotropics should therefore not be guided by TDCCO in this setting.