RESUMEN
Introduction: Bone marrow embolization may complicate orthopedic surgery, potentially causing fat embolism syndrome. The inflammatory potential of bone marrow emboli is unclear. We aimed to investigate the inflammatory response to femoral intramedullary nailing, specifically the systemic inflammatory effects in plasma, and local tissue responses. Additionally, the plasma response was compared to that following intravenous injection of autologous bone marrow. Methods: Twelve pigs underwent femoral nailing (previously shown to have fat emboli in lung and heart), four received intravenous bone marrow, and four served as sham controls. Blood samples were collected hourly and tissue samples postmortem. Additionally, we incubated bone marrow and blood, separately and in combination, from six pigs in vitro. Complement activation was detected by C3a and the terminal C5b-9 complement complex (TCC), and the cytokines TNF, IL-1ß, IL-6 and IL-10 as well as the thrombin-antithrombin complexes (TAT) were all measured using enzyme-immunoassays. Results: After nailing, plasma IL-6 rose 21-fold, compared to a 4-fold rise in sham (p=0.0004). No plasma differences in the rest of the inflammatory markers were noted across groups. However, nailing yielded 2-3-times higher C3a, TCC, TNF, IL-1ß and IL-10 in lung tissue compared to sham (p<0.0001-0.03). Similarly, heart tissue exhibited 2-times higher TCC and IL-1ß compared to sham (p<0.0001-0.03). Intravenous bone marrow yielded 8-times higher TAT than sham at 30 minutes (p<0.0001). In vitro, incubation of bone marrow for four hours resulted in 95-times higher IL-6 compared to whole blood (p=0.03). Discussion: A selective increase in plasma IL-6 was observed following femoral nailing, whereas lung and heart tissues revealed a broad local inflammatory response not reflected systemically. In vitro experiments may imply bone marrow to be the primary IL-6 source.
Asunto(s)
Embolia Grasa , Interleucina-6 , Pulmón , Animales , Porcinos , Interleucina-6/sangre , Embolia Grasa/etiología , Embolia Grasa/sangre , Embolia Grasa/inmunología , Pulmón/inmunología , Pulmón/patología , Pulmón/metabolismo , Médula Ósea/metabolismo , Fijación Intramedular de Fracturas/efectos adversos , Miocardio/metabolismo , Miocardio/patología , Miocardio/inmunología , Inflamación/sangre , Inflamación/inmunología , Femenino , Citocinas/sangre , Citocinas/metabolismo , Clavos Ortopédicos , Activación de Complemento , Fémur/metabolismo , Modelos Animales de EnfermedadRESUMEN
Background: Transcatheter interventions are increasingly used in children with congenital heart disease. However, these interventions can affect cardiac output and cerebral circulation. In this pilot study, we aimed to investigate the use of NeoDoppler, a continuous transfontanellar cerebral Doppler monitoring system, to evaluate the impact of transcatheter interventions on cerebral circulation. Methods: Nineteen participants under one year of age (mean age 3.5 months) undergoing transcatheter cardiac interventions were prospectively included. Transfontanellar cerebral Doppler monitoring with the NeoDoppler system was initiated after intubation and continued until the end of the procedure. Results: Instant detection of changes in cerebral blood flow were observed across a spectrum of transcatheter interventions. Balloon aortic valvuloplasty demonstrated temporary cessation of cerebral blood flow during balloon inflation. Increase in cerebral diastolic blood flow velocity and decreased pulsatility were observed during patent ductus arteriosus occlusion. Changes in cerebral blood flow patterns were detected in two patients who encountered complications during their transcatheter interventions. There was no significant change in Doppler parameters before and after the interventions for the entire patient group. High quality recordings were achieved in 87.3% of the monitoring period. Conclusions: Continuous transfontanellar cerebral Doppler is feasible in monitoring cerebral hemodynamic trends and shows instantaneous changes associated with interventions and complications. It could become a useful monitoring tool during transcatheter interventions in infants.
RESUMEN
BACKGROUND: In this pilot study, we investigated continuous cerebral blood flow velocity measurements to explore cerebrovascular hemodynamics in infants with congenital heart disease undergoing cardiac surgery. METHODS: A non-invasive transfontanellar cerebral Doppler monitor (NeoDoppler) was used to monitor 15 infants (aged eight days to nine months) during cardiac surgery with cardiopulmonary bypass. Numerical and visual analyses were conducted to assess trends and events in Doppler measurements together with standard monitoring equipment. The mean flow index, calculated as the moving Pearson correlation between mean arterial pressure and time averaged velocity, was utilized to evaluate dynamic autoregulation. Two levels of impaired autoregulation were defined (Mean flow index >0.3/0.45), and percentage of time above these limits were calculated. RESULTS: High quality recordings were achieved during 90.6% of the monitoring period. There was a significant reduction in time averaged velocity in all periods of cardiopulmonary bypass. All patients showed a high percentage of time with impaired dynamic autoregulation, with Mean flow index >0.3 and 0.45: 73.71% ± 9.06% and 65.16% ± 11.27% respectively. Additionally, the system promptly detected hemodynamic events. CONCLUSION: Continuous transfontanellar cerebral Doppler monitoring could become an additional tool in enhancing cerebral monitoring in infants during cardiac surgery. IMPACT: This pilot study demonstrates the feasibility of continuous transfontanellar Doppler monitoring of cerebral blood flow velocities during cardiac surgery in infants. It also demonstrates a high proportion of time with impaired cerebral autoregulation during cardiac surgery based on the Mean flow index. Continuous transfontanellar Doppler could become a useful tool to improve cerebral monitoring and provide new pathophysiological insight.
RESUMEN
Background: Shaft fractures of the femur are commonly treated with intramedullary nailing, which can release bone marrow emboli into the bloodstream. Emboli can travel to the lungs, impairing gas exchange and causing inflammation. Occasionally, emboli traverse from the pulmonary to the systemic circulation, hindering perfusion and resulting in injuries such as heart and brain infarctions, known as fat embolism syndrome. We studied the extent of systemic bone marrow embolization in a pig model. Methods: Twelve anesthetized pigs underwent bilateral intramedullary nailing of the femur, while 3 animals served as sham controls. Monitoring included transesophageal echocardiography (TEE), pulse oximetry, electrocardiography, arterial blood pressure measurement, and blood gas and troponin-I analysis. After surgery, animals were monitored for 240 minutes before euthanasia. Post mortem, the heart, lungs, and brain were biopsied. Results: Bone marrow emboli were found in the heart and lungs of all 12 of the pigs that underwent intramedullary nailing and in the brains of 11 of them. No emboli were found in the sham group. The pigs subjected to intramedullary nailing exhibited significant hypoxia (PaO2/FiO2 ratio, 410 mm Hg [95% confidence interval (CI), 310 to 510) compared with the sham group (594 mm Hg [95% CI, 528 to 660]). The nailing group exhibited ST-segment alterations consistent with myocardial ischemia and a significant increase in the troponin-I level compared with the sham group (1,580 ng/L [95% CI, 0 to 3,456] versus 241 ng/L [95% CI, 0 to 625] at the 240-minute time point; p = 0.005). TEE detected emboli in the right ventricular outflow tract, but not systemically, in the nailing group. Conclusions: Bilateral intramedullary nailing caused bone marrow emboli in the lungs and systemic emboli in the heart and brain in this pig model. The observed clinical manifestations were consistent with coronary and pulmonary emboli. TEE detected pulmonary but not systemic embolization. Clinical Relevance: Femoral intramedullary nailing in humans is likely to result in embolization as described in our pig model. Focused monitoring is necessary for detection of fat embolism syndrome. Absence of visual emboli in the left ventricle on TEE does not exclude the occurrence of systemic bone marrow emboli.
RESUMEN
Background: A cerebroprotective effect of low frequency oscillations (LFO) in cerebral blood flow (CBF) has been suggested in adults, but its significance in neonates is not known. This observational study evaluates normal arterial and venous cerebral blood flow in healthy neonates using NeoDoppler, a novel Doppler ultrasound system which can measure cerebral hemodynamics continuously. Method: Ultrasound Doppler data was collected for 2â h on the first and second day of life in 36 healthy term born neonates. LFO (0.04-0.15â Hz) were extracted from the velocity curve by a bandpass filter. An angle independent LFO index was calculated as the coefficient of variation of the filtered curve. Separate analyses were done for arterial and venous signals, and results were related to postnatal age and behavioral state (asleep or awake). Results: The paper describes normal physiologic variations of arterial and venous cerebral hemodynamics. Mean (SD) arterial and venous LFO indices (%) were 6.52 (2.55) and 3.91 (2.54) on day one, and 5.60 (1.86) and 3.32 (2.03) on day two. After adjusting for possible confounding factors, the arterial LFO index was estimated to decrease by 0.92 percent points per postnatal day (p < 0.001). The venous LFO index did not change significantly with postnatal age (p = 0.539). Arterial and venous LFO were not notably influenced by behavioral state. Conclusion: The results indicate that arterial LFO decrease during the first 2 days of life in healthy neonates. This decrease most likely represents normal physiological changes related to the transitional period. A similar decrease for venous LFO was not found.
RESUMEN
There is a risk of gaseous and solid micro-embolus formation during transcatheter cardiac interventions and surgery in children with congenital heart disease (CHD). Our aim was to study the burden of high-intensity transient signals (HITS) during these procedures in infants. We used a novel color M-mode Doppler (CMD) technique by NeoDoppler, a non-invasive ultrasound system based on plane wave transmissions for transfontanellar continuous monitoring of cerebral blood flow in infants. The system displays CMD with 24 sample volumes and a Doppler spectrogram. Infants with CHD undergoing transcatheter interventions (n = 15) and surgery (n = 13) were included. HITS were manually detected based on an "embolic signature" in the CMD with corresponding intensity increase in the Doppler spectrogram. Embolus-to-blood ratio (EBR) defined HITS size. A total of 1169 HITS with a median EBR of 9.74 dB (interquartile range [IQR]: 5.10-15.80 dB) were detected. The median number of HITS in the surgery group was 45 (IQR: 11-150), while in the transcatheter group the median number was 12 (IQR: 7-24). During cardiac surgery, the highest number of HITS per hour was seen from initiation of cardiopulmonary bypass to aortic X-clamp. In this study we detected frequent HITS and determined the feasibility of using NeoDoppler monitoring for HITS detection.