Procedural sedation and analgesia versus nerve blocks for reduction of fractures and dislocations in the emergency department: A systematic review and meta-analysis.

Background: Procedural sedation and analgesia (PSA) and peripheral nerve blocks (NBs) are techniques to manage pain and facilitate reduction of dislocated joints or fractures. However, it is unclear if either approach provides any distinct advantage in the emergency department (ED). The aim of this systematic review is to compare these 2 techniques on pain scores, adverse events, patient satisfaction, and length of stay (LOS) in the ED. Methods: We performed an electronic search of MEDLINE, EMBASE, and the Cochrane Library, and references were hand-searched. Randomized controlled trials (RCTs) comparing PSA with NBs for orthopedic reductions in the ED were included. Outcomes of interest included pain scores, adverse events, patient satisfaction, and LOS in the ED. A total of 2 reviewers independently screened abstracts and extracted data into a standardized form. The Cochrane risk-of-bias tool was used to evaluate study quality. The Grading of Recommendation Assessment Development and Evaluation approach was used to assess the certainty and strength of the evidence. Data on pain scores were pooled using a random-effects model and are reported as standardized mean differences (SMDs) with 95% confidence intervals (CIs). Results: A total of 6 RCTs (n = 256) were included in a qualitative review, and 4 RCTs (n = 101) were included in the meta-analysis. There was no significant difference in pain scores between the PSA and NB groups (P = 0.47; SMD, 0.45; 95% CI, -0.78 to 1.69; I2 = 0.94). There were less adverse events in the NB group (0%-3.3%) compared with the PSA group (0%-20%; n = 256). LOS times were consistently shorter in the NB group (n = 215). Patient satisfaction was comparable in both groups (n = 196). Conclusion: Based on the available evidence, NBs performed by emergency physicians are as effective as PSA in managing pain during orthopedic reductions in the ED. NBs are associated with fewer adverse events and shorter LOS in the ED. The quality of evidence is low.

C-Reactive Protein, Procalcitonin, and White Blood Count to Rule Out Neonatal Early-onset Sepsis Within 36 Hours: A Secondary Analysis of the Neonatal Procalcitonin Intervention Study.

BACKGROUND: Neonatal early-onset sepsis (EOS) is one of the main causes of global neonatal mortality and morbidity, and initiation of early antibiotic treatment is key. However, antibiotics may be harmful. METHODS: We performed a secondary analysis of results from the Neonatal Procalcitonin Intervention Study, a prospective, multicenter, randomized, controlled intervention study. The primary outcome was the diagnostic accuracy of serial measurements of C-reactive protein (CRP), procalcitonin (PCT), and white blood count (WBC) within different time windows to rule out culture-positive EOS (proven sepsis). RESULTS: We analyzed 1678 neonates with 10 899 biomarker measurements (4654 CRP, 2047 PCT, and 4198 WBC) obtained within the first 48 hours after the start of antibiotic therapy due to suspected EOS. The areas under the curve (AUC) comparing no sepsis vs proven sepsis for maximum values of CRP, PCT, and WBC within 36 hours were 0.986, 0.921, and 0.360, respectively. The AUCs for CRP and PCT increased with extended time frames up to 36 hours, but there was no further difference between start to 36 hours vs start to 48 hours. Cutoff values at 16 mg/L for CRP and 2.8 ng/L for PCT provided a sensitivity of 100% for discriminating no sepsis vs proven sepsis. CONCLUSIONS: Normal serial CRP and PCT measurements within 36 hours after the start of empiric antibiotic therapy can exclude the presence of neonatal EOS with a high probability. The negative predictive values of CRP and PCT do not increase after 36 hours.

Availability and quality of procedural sedation and analgesia in emergency departments without emergency physicians: A national survey in the Netherlands.

BACKGROUND: Emergency physicians have been successful in implementing procedural sedation and analgesia (PSA) to treat emergency department (ED) patients who need to undergo painful procedures. However, 25% of the EDs in the Netherlands are not staffed by emergency physicians. The aim of this study was to investigate PSA availability and quality in EDs without emergency physicians. METHODS: We performed an exploratory cross-sectional study amongst ED nurses and physicians in all 13 EDs without emergency physicians in the Netherlands. Data were gathered using a standardized questionnaire. RESULTS: The response rate was 34.3% (148/432). Of the respondents, 84/148 (56.8%) provided adult PSA and 30/148 (20.3%) provided paediatric PSA. Main reasons for not providing PSA were insufficient numbers of trained staff to support PSA in the ED and insufficient training and exposure. The providers agreed significantly stronger when reflecting their PSA competencies in adults compared to paediatric patients. CONCLUSION: The key to improve pain management in the ED-setting may lay in investing in continuous training of ED health care professionals and/or acquiring professionals who are both qualified in PSA and available in the ED.

Paediatric procedural sedation and analgesia by emergency physicians in a country with a recent establishment of emergency medicine.

OBJECTIVES: Paediatric patients receive less procedural sedation and analgesia (PSA) in the emergency department compared with adults, especially in countries where emergency medicine is at an early stage of development. The objectives of this study were to evaluate the adverse events and efficacy of paediatric PSA in a country with a recent establishment of emergency medicine and to describe which factors aided implementation. METHODS: This is a prospective, multicentre, observational study of paediatric patients undergoing PSA by the first trained emergency physicians (EPs) in The Netherlands. A standardized data collection form was used at all participating hospitals to collect data on adverse events, amnesia, pain scores, and procedure completion. A survey was used to interpret which factors had aided PSA implementation. RESULTS: We recorded 351 paediatric PSA. The mean age was 9.5 years (95% confidence interval: 9.1-10.0). Esketamine was most frequently used (42.4%), followed by propofol (34.7%). The adverse event rate was low (3.0%). Amnesia was present in 86.8%. The median pain score was 2 (out of 10) for patients without amnesia. Procedures were successfully completed in 93.9% of the cases. CONCLUSION: Paediatric PSA provided by the first EPs in The Netherlands showed appropriate levels of sedation and analgesia with a high rate of procedure completion and a low rate of adverse events. Our paper suggests that EPs provided with a proper infrastructure of mentorship, training and guidelines can implement effective paediatric PSA.

Procedural sedation and analgesia practices by emergency physicians in the Netherlands: a nationwide survey.

BACKGROUND: Several efforts have been made to assure and to improve the quality of procedural sedation and analgesia (PSA) performed by emergency physicians (EPs) in The Netherlands. This study investigated the current PSA practice and competences of EPs in both adult and paediatric patients. In particular, if residency and current training, awareness of guidelines is sufficient for registered EPs to adequately perform PSA and if the availability of both adult and paediatric PSA in the ED is adequate. METHODS: A cross-sectional nationwide survey was performed amongst Dutch EPs (n = 463) in June 2016. We collected data on background, training, practice, and competencies of both adult and paediatric PSA. We investigated guideline adherence, reasons for not performing PSA, and desired improvements. RESULTS: The respondents (n = 191) represented 84.6% hospitals with EPs and 41.3% of all EPs in The Netherlands. Nearly all EPs (97.8%) performed PSA in adult patients compared to only 59.1% who performed PSA in paediatric patients (p < 0.001). The major reason for not performing paediatric PSA was caused by a lack of exposure during the training-program (74.1%). PSA-guideline knowledge (98.3%) and PSA related adverse event registration (98.3%) were excellent. Lack of 24/7-availability of both adult and paediatric emergency department PSA was mainly caused by a shortage of EPs. Self-reflection indicated that EPs feel less competent in performing paediatric PSA when compared to adult PSA. CONCLUSION: This nationwide survey demonstrates that there is still a significant gap between the performance of adult and paediatric PSA even though guideline adherence and registration of PSA-related adverse events appear to be adequate. Enhancement of paediatric PSA training in combination with an increase of EP-staffing can help improve the availability of adult and paediatric PSA in the emergency department.

[Gastric volvulus in children]. / Maagvolvulus bij kinderen.

BACKGROUND: Gastric volvulus in children is rare and can be life-threatening if not recognised in time. CASE DESCRIPTION: A 3.5-year-old boy presented to his GP with severe, non-bilious vomiting, abdominal distension and abdominal pain. Additional diagnostic tests showed hypochloraemic alkalosis and abdominal ultrasonography suggested gastric volvulus. A barium study showed slow passage of contrast into the duodenum combined with craniomedial displacement of the duodenum. This image matches that of mesenteroaxial gastric volvulus. The diagnosis was confirmed during surgery and gastropexy was successfully performed. CONCLUSION: The diagnosis of gastric volvulus can be difficult. Easily accessible additional diagnostics in the form of ultrasonography, possibly followed by a barium study, may be helpful.

[A child with primary sclerosing cholangitis]. / Een kind met primaire scleroserende cholangitis.

BACKGROUND: Primary sclerosing cholangitis is a rare liver disease which is mainly diagnosed in adults. This chronic progressive disease, characterised by inflammation, fibrosis and strictures of the intra- and extrahepatic bile ducts, leads to cirrhosis. There is a strong association between primary sclerosing cholangitis and inflammatory bowel disease (IBD). CASE DESCRIPTION: A 10-year-old boy presented at the accident and emergency department with fever, episodes of abdominal pain, nausea, vomiting, fatigue and hepatomegaly. Blood tests, pathology investigations, liver biopsy and magnetic resonance cholangiopancreatography (MRCP) led to the diagnosis of primary sclerosing cholangitis. The patient was treated with ursodeoxycholic acid and later, because of unbearable itching, sequentially with lidocaine 3% ointment, rifampicin, an endoprosthesis in the common bile duct and glucocorticoids. One year later he returned to the paediatrician with abdominal pain and bloody diarrhoea. Endoscopy revealed features of indeterminate colitis. Remission of the disease was achieved quickly after treatment with mesalazine. CONCLUSION: Primary sclerosing cholangitis can develop in childhood and is often associated with IBD.

Talking with parents about end-of-life decisions for their children.

BACKGROUND AND OBJECTIVE: Retrospective studies show that most parents prefer to share in decisions to forgo life-sustaining treatment (LST) from their children. We do not yet know how physicians and parents communicate about these decisions and to what extent parents share in the decision-making process. METHODS: We conducted a prospective exploratory study in 2 Dutch University Medical Centers. RESULTS: Overall, 27 physicians participated, along with 37 parents of 19 children for whom a decision to withhold or withdraw LST was being considered. Forty-seven conversations were audio recorded, ranging from 1 to 8 meetings per patient. By means of a coding instrument we quantitatively and qualitatively analyzed physicians' and parents' communicative behaviors. On average, physicians spoke 67% of the time, parents 30%, and nurses 3%. All physicians focused primarily on providing medical information, explaining their preferred course of action, and informing parents about the decision being reached by the team. Only in 2 cases were parents asked to share in the decision-making. Despite their intense emotions, most parents made great effort to actively participate in the conversation. They did this by asking for clarifications, offering their preferences, and reacting to the decision being proposed (mostly by expressing their assent). In the few cases where parents strongly preferred LST to be continued, the physicians either gave parents more time or revised the decision. CONCLUSIONS: We conclude that parents are able to handle a more active role than they are currently being given. Parents' greatest concern is that their child might suffer.

[A boy with cervical focal myositis]. / Een jongen met focale myositis in de hals.

BACKGROUND: Focal myositis is a rare idiopathic pseudotumour that mostly occurs in the extremities in adults. CASE DESCRIPTION: An 8-year-old boy presented with a few months history of swelling in the neck and fever. Ultrasound investigation revealed an inhomogenous mass consistent with lymphadenitis. After nine days of antibiotic therapy, the clinical picture of fever and swelling was unchanged. MRI imaging revealed continuity of the swelling in the sternocleidomastoid muscle and a malignant process was suspected. Microscopy showed no malignant cells, however, but a lymphoplasmocytic infiltration with fibrosis and degeneration of muscle fibres, consistent with focal myositis. No intervention was undertaken and one year after presentation the tumour had regressed almost entirely. CONCLUSION: Focal myositis can present as a cervical tumour. On ultrasound, the condition is hard to distinguish from lymphadenopathy or malignancy. In cases of insufficient response to empirical antibiotic therapy, focal myositis should be considered.

Aggravation of myocardial dysfunction by injurious mechanical ventilation in LPS-induced pneumonia in rats.

BACKGROUND: Mechanical ventilation (MV) may cause ventilator-induced lung injury (VILI) and may thereby contribute to fatal multiple organ failure. We tested the hypothesis that injurious MV of lipopolysaccharide (LPS) pre-injured lungs induces myocardial inflammation and further dysfunction ex vivo, through calcium (Ca2+)-dependent mechanism. MATERIALS AND METHODS: N = 35 male anesthetized and paralyzed male Wistar rats were randomized to intratracheal instillation of 2 mg/kg LPS or nothing and subsequent MV with lung-protective settings (low tidal volume (Vt) of 6 mL/kg and 5 cmH2O positive end-expiratory pressure (PEEP)) or injurious ventilation (high Vt of 19 mL/kg and 1 cmH2O PEEP) for 4 hours. Myocardial function ex vivo was evaluated in a Langendorff setup and Ca2+ exposure. Key mediators were determined in lung and heart at the mRNA level. RESULTS: Instillation of LPS and high Vt MV impaired gas exchange and, particularly when combined, increased pulmonary wet/dry ratio; heat shock protein (HSP)70 mRNA expression also increased by the interaction between LPS and high Vt MV. For the heart, C-X-C motif ligand (CXCL)1 and Toll-like receptor (TLR)2 mRNA expression increased, and ventricular (LV) systolic pressure, LV developed pressure, LV +dP/dtmax and contractile responses to increasing Ca2+ exposure ex vivo decreased by LPS. High Vt ventilation aggravated the effects of LPS on myocardial inflammation and dysfunction but not on Ca2+ responses. CONCLUSIONS: Injurious MV by high Vt aggravates the effects of intratracheal instillation of LPS on myocardial dysfunction, possibly through enhancing myocardial inflammation via pulmonary release of HSP70 stimulating cardiac TLR2, not involving Ca2+ handling and sensitivity.

Salutary effect of resveratrol on sepsis-induced myocardial depression.

OBJECTIVES: We hypothesized that resveratrol administration would reverse sepsis-dependent downregulation of peroxisome proliferator activated receptor-γ coactivator 1α, preserve mitochondrial integrity, and rescue animals from sepsis-induced myocardial failure. SETTING: Teaching hospital research laboratory. INTERVENTIONS: Cecal ligation and puncture in mice was performed to induce sepsis. Mice that underwent cecal ligation and puncture were randomly assigned to receive resveratrol (30 mg/kg or 60 mg/kg) or vehicle 1 mL sodium chloride 0.9% subcutaneously in the scruff of the neck directly after surgery and at 16, 24, and 40 hrs, respectively. MEASUREMENTS AND RESULTS: Forty-eight hrs after cecal ligation and puncture, cardiac performance was established using echocardiography. Mitochondrial integrity was evaluated with electron microscopy, and changes in gene expression were evaluated with microarray analysis. Survival at 48 hrs was just under 50% and comparable between groups. Myocardial contractile function significantly improved after resveratrol treatment. Resveratrol-treated mice developed focal areas of edema, whereas vehicle-treated mice developed significant, diffuse myocardial edema. Electron microscopy revealed widespread swollen mitochondria with ruptured outer membranes, autophagosomes, and vacuolation of the internal compartment, which were significantly attenuated in resveratrol-treated animals. Resveratrol treatment significantly increased cardiac expression of peroxisome proliferator-activated receptor-γ coactivator 1a. Microarray analysis revealed that resveratrol treatment resulted in upregulation of the peroxisome proliferator-activated receptor-γ coactivator gene set containing genes known to be regulated by this transcriptional coactivator. Our data strongly suggest that administration of resveratrol modulates bioenergy metabolism, substrate utilization, oxidative stress, and detoxification pathways associated with both mitochondrial and cardiac pathological conditions, but does not alter mortality from sepsis. CONCLUSIONS: The salutary effects of resveratrol on cecal ligation and puncture-induced myocardial dysfunction are associated with increased peroxisome proliferator-activated receptor-γ coactivator 1a abundance and function. Preservation of myocardial energy production capacity, prevention of secondary injury, mitigation of inflammation, and reversal of sepsis-induced myocardial remodeling are likely to underlie its beneficial effects. This however, does not result in improved survival.

Early myocardial dysfunction is not caused by mitochondrial abnormalities in a rat model of peritonitis.

BACKGROUND: Patients with complicated intra-abdominal infections are prone to develop multiple organ failure, including myocardial dysfunction. We hypothesized that early dysfunction during sepsis is associated with inflammation, mitochondrial injury, impaired mitochondrial function, and activation of mitochondrial biogenesis. MATERIALS AND METHODS: Rats received lipopolysaccharide (LPS, n = 11) intraperitoneally. Healthy rats (n = 6) served as controls. Myocardial function was measured ex vivo in an isolated Langendorff-perfused heart set-up. Myocardial vascular cell adhesion molecule-1 (VCAM-1) expression was determined by immunofluorescence microscopy. Cytochrome c release and cytochrome c oxidase (COX IV) activity were measured by immunohistochemistry and enzyme histochemistry, respectively. Protein expression of tumor necrosis factor-α (TNF-α), B-cell lymphoma (Bcl)-2, peroxisome proliferator activated receptor γ cofactor 1α (PGC-1α), and mitochondrial transcription factor A (TFAM) were analyzed by Western blot technique. Mitochondria were studied by electron microscopy. RESULTS: Two hours after LPS injection, developed pressure had decreased and after 4 h myocardial contractility (+dP/dt) and relaxation (-dP/dt) also had decreased. TNF-α protein expression was increased after 2 h and returned to normal at 4 h, whereas after 4 h VCAM-1 expression was higher in LPS-treated animals. At 2 h a substrate-dependent increase in COXIV-activity was seen, but no mitochondrial damage occurred as cytochrome c release, COX IV activity and Bcl-2, PGC-1α or TFAM expression were not changed. Electron microscopy did not reveal differences in myocardial mitochondrial characteristics between LPS-treated and control rats. CONCLUSIONS: Early myocardial dysfunction in sepsis is associated with myocardial inflammation but not with mitochondrial injury, impaired mitochondrial function, or activated mitochondrial biogenesis.

High tidal volume mechanical ventilation-induced lung injury in rats is greater after acid instillation than after sepsis-induced acute lung injury, but does not increase systemic inflammation: an experimental study.

BACKGROUND: To examine whether acute lung injury from direct and indirect origins differ in susceptibility to ventilator-induced lung injury (VILI) and resultant systemic inflammatory responses. METHODS: Rats were challenged by acid instillation or 24 h of sepsis induced by cecal ligation and puncture, followed by mechanical ventilation (MV) with either a low tidal volume (Vt) of 6 mL/kg and 5 cm H2O positive end-expiratory pressure (PEEP; LVt acid, LVt sepsis) or with a high Vt of 15 mL/kg and no PEEP (HVt acid, HVt sepsis). Rats sacrificed immediately after acid instillation and non-ventilated septic animals served as controls. Hemodynamic and respiratory variables were monitored. After 4 h, lung wet to dry (W/D) weight ratios, histological lung injury and plasma mediator concentrations were measured. RESULTS: Oxygenation and lung compliance decreased after acid instillation as compared to sepsis. Additionally, W/D weight ratios and histological lung injury scores increased after acid instillation as compared to sepsis. MV increased W/D weight ratio and lung injury score, however this effect was mainly attributable to HVt ventilation after acid instillation. Similarly, effects of HVt on oxygenation were only observed after acid instillation. HVt during sepsis did not further affect oxygenation, compliance, W/D weight ratio or lung injury score. Plasma interleukin-6 and tumour necrosis factor-α concentrations were increased after acid instillation as compared to sepsis, but plasma intercellular adhesion molecule-1 concentration increased during sepsis only. In contrast to lung injury parameters, no additional effects of HVt MV after acid instillation on plasma mediator concentrations were observed. CONCLUSIONS: During MV more severe lung injury develops after acid instillation as compared to sepsis. HVt causes VILI after acid instillation, but not during sepsis. However, this differential effect was not observed in the systemic release of mediators.

The process of end-of-life decision-making in pediatrics: a national survey in the Netherlands.

OBJECTIVE: The goal of this study was to investigate how Dutch pediatric specialists reach end-of-life decisions, how they involve parents, and how they address conflicts. METHODS: We conducted a national cross-sectional survey among pediatric intensivists, oncologists, neurologists, neurosurgeons, and metabolic pediatricians practicing in the 8 Dutch university hospitals. We collected information on respondents' overall opinions and their clinical practice. RESULTS: Of the 185 eligible pediatric specialists, 74% returned the questionnaire. All responding physicians generally discuss an end-of-life decision with colleagues before discussing it with parents. In half of the reported cases, respondents informed parents about the intended decision and asked their permission. In one-quarter of the cases, respondents informed parents without asking for their permission. In the remaining one-quarter of the cases, respondents advised parents and consequently allowed them to have the decisive voice. The chosen approach is highly influenced by type of decision and type and duration of treatment. Conflicts within medical teams arose as a result of uncertainties about prognosis and treatment options. Most conflicts with parents arose because parents had a more positive view of the prognosis or had religious objections to treatment discontinuation. All conflicts were eventually resolved by a combination of strategies. In 66% of all cases, pain and symptom management were intensified before the child's death. CONCLUSIONS: Within Dutch pediatrics, end-of-life decisions are team decisions. Pediatric specialists differ considerably in how they involve parents in end-of-life decision-making, ranging from benevolent paternalism to parental autonomy. Main conflict-solving strategies are taking more time and extending discussions.

Renal hypoperfusion and impaired endothelium-dependent vasodilation in an animal model of VILI: the role of the peroxynitrite-PARP pathway.

INTRODUCTION: Mechanical ventilation (MV) can injure the lungs and contribute to an overwhelming inflammatory response, leading to acute renal failure (ARF). We previously showed that poly(adenosine diphosphate-ribose) polymerase (PARP) is involved in the development of ventilator-induced lung injury (VILI) and the related ARF, but the mechanisms underneath remain unclear. In the current study we therefore tested the hypothesis that renal blood flow and endothelial, functional and tissue changes in the kidney of rats with lipopolysaccharide (LPS)-induced lung injury aggravated by MV, is caused, in part, by activation of PARP by peroxynitrite. METHODS: Anesthetized Sprague Dawley rats (n = 31), were subjected to intratracheal instillation of lipopolysaccharide at 10 mg/kg followed by 210 min of mechanical ventilation at either low tidal volume (6 mL/kg) with 5 cm H2O positive end-expiratory pressure or high tidal volume (19 mL/kg) with zero positive end-expiratory pressure in the presence or absence of a peroxynitrite decomposition catalyst, WW85 or a PARP inhibitor, PJ-34. During the experiment, hemodynamics and blood gas variables were monitored. At time (t) t = 0 and t = 180 min, renal blood flow was measured. Blood and urine were collected for creatinine clearance measurement. Arcuate renal arteries were isolated for vasoreactivity experiment and kidneys snap frozen for staining. RESULTS: High tidal volume ventilation resulted in lung injury, hypotension, renal hypoperfusion and impaired renal endothelium-dependent vasodilation, associated with renal dysfunction and tissue changes (leukocyte accumulation and increased expression of neutrophil gelatinase-associated lipocalin). Both WW85 and PJ-34 treatments attenuated lung injury, preserved blood pressure, attenuated renal endothelial dysfunction and maintained renal blood flow. In multivariable analysis, renal blood flow improvement was, independently from each other, associated with both maintained blood pressure and endothelium-dependent vasodilation by drug treatment. Finally, drug treatment improved renal function and reduced tissue changes. CONCLUSIONS: The peroxynitrite-induced PARP activation is involved in renal hypoperfusion, impaired endothelium-dependent vasodilation and resultant dysfunction, and injury, in a model of lung injury.

Production of endothelin-1 and reduced blood flow in the rat kidney during lung-injurious mechanical ventilation.

INTRODUCTION: The mechanisms by which mechanical ventilation (MV) can injure remote organs, such as the kidney, remain poorly understood. We hypothesized that upregulation of systemic inflammation, as reflected by plasma interleukin-6 (IL-6) levels, in response to a lung-injurious ventilatory strategy, ultimately results in kidney dysfunction mediated by local endothelin-1 (ET-1) production and renal vasoconstriction. METHODS: Healthy, male Wistar rats were randomized to 1 of 2 MV settings (n=9 per group) and ventilated for 4 h. One group had a lung-protective setting using peak inspiratory pressure of 14 cm H2O and a positive end-expiratory pressure of 5 cm H2O; the other had a lung-injurious strategy using a peak inspiratory pressure of 20 cm H2O and positive end-expiratory pressure of 2 cm H2O. Nine randomly assigned rats served as nonventilated controls. We measured venous and arterial blood pressure and cardiac output (thermodilution method), renal blood flow (RBF) using fluorescent microspheres, and calculated creatinine clearance, urine flow, and fractional sodium excretion. Histological lung damage was assessed using hematoxylin-eosin staining. Renal ET-1 and plasma ET-1 and IL-6 concentrations were measured using enzyme-linked immunosorbent assays. RESULTS: Lung injury scores were higher after lung-injurious MV than after lung-protective ventilation or in sham controls. Lung-injurious MV resulted in significant production of renal ET-1 compared with the lung-protective and control groups. Simultaneously, RBF in the lung-injurious MV group was approximately 40% lower (P<0.05) than in the control group and 28% lower (P<0.05) than in the lung-protective group. Plasma ET-1 and IL-6 levels did not differ among the groups and systemic hemodynamics, such as cardiac output, were comparable. There was no effect on creatinine clearance, fractional sodium excretion, urine output, or kidney histology. CONCLUSIONS: Lung-injurious MV for 4 h in healthy rats results in significant production of renal ET-1 and in decreased RBF, independent of IL-6. Decreased RBF has no observable effect on kidney function or histology.

Incidence and risk factors of prolonged mechanical ventilation in neuromuscular scoliosis surgery.

Patients with neuromuscular scoliosis (NMS) are frequently considered at high risk for postoperative complications based on their underlying disease and comorbidities. Postoperative complications include prolonged mechanical ventilation (MV), defined longer than 72 h, at the paediatric intensive care unit. The objectives of this retrospective study were to assess the incidence of prolonged MV in patients with NMS following scoliosis surgery and to identify predictive risk factors. A total of 46 consecutive patients underwent surgical spinal fusion and instrumentation for progressive NMS. Prolonged MV was required in seven of 46 patients (15%). The only risk factor for prolonged MV was a decreased preoperative pulmonary function. Forced expired volume in 1 s and vital capacity were significantly decreased in patients with MV >72 h compared with patients with MV <72 h. Routine preoperative pulmonary function testing may reveal important information with regard to restrictive lung disease in the preoperative assessment of patients with NMS and predict the early postoperative clinical course.

Inhibition of poly(adenosine diphosphate-ribose) polymerase attenuates ventilator-induced lung injury.

BACKGROUND: Mechanical ventilation can induce organ injury associated with overwhelming inflammatory responses. Excessive activation of poly(adenosine diphosphate-ribose) polymerase enzyme after massive DNA damage may aggravate inflammatory responses. Therefore, the authors hypothesized that the pharmacologic inhibition of poly(adenosine diphosphate-ribose) polymerase by PJ-34 would attenuate ventilator-induced lung injury. METHODS: Anesthetized rats were subjected to intratracheal instillation of lipopolysaccharide at a dose of 6 mg/kg. The animals were then randomly assigned to receive mechanical ventilation at either low tidal volume (6 ml/kg) with 5 cm H2O positive end-expiratory pressure or high tidal volume (15 ml/kg) with zero positive end-expiratory pressure, in the presence and absence of intravenous administration of PJ-34. RESULTS: The high-tidal-volume ventilation resulted in an increase in poly(adenosine diphosphate-ribose) polymerase activity in the lung. The treatment with PJ-34 maintained a greater oxygenation and a lower airway plateau pressure than the vehicle control group. This was associated with a decreased level of interleukin 6, active plasminogen activator inhibitor 1 in the lung, attenuated leukocyte lung transmigration, and reduced pulmonary edema and apoptosis. The administration of PJ-34 also decreased the systemic levels of tumor necrosis factor alpha and interleukin 6, and attenuated the degree of apoptosis in the kidney. CONCLUSION: The pharmacologic inhibition of poly(adenosine diphosphate-ribose) polymerase reduces ventilator-induced lung injury and protects kidney function.

Red blood cell transfusion in critically ill children is independently associated with increased mortality.

OBJECTIVE: To test the hypothesis that RBC transfusion in critically ill children is independently associated with increased mortality and morbidity. DESIGN: Retrospective, descriptive epidemiologic cohort study. SETTING: Single-center experience of a nine-bed pediatric intensive care unit (PICU) facility. PATIENTS: Critically ill children without ongoing active blood loss aged 0[Symbol: see text]months to 18[Symbol: see text]years, excluding prematurely born infants or patients after cardiothoracic surgery, and patients with chronic anemia. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Data of 295 consecutive patients was studied. Of these patients, 13.4% had a Hb concentration less than 9.6 g/dl. Sixty-seven (22.7%) of all patients were transfused, 39 only once. Transfused patients had a higher mortality (16.4 vs. 2.6%, p < 0.001). Mortality seemed related to the number of transfusion (p = 0.002) rather than the pre-transfusion Hb concentration (p = 0.10). Transfused patients required prolonged ventilatory support (11.1 +/- 1.8 vs. +/- 0.3 days, p < 0.001), infusion of vaso-active agents (8.2 +/- 1.8 vs. 2.8 +/- 0.6 days, p < 0.001) and PICU stay (13.0 +/- 1.8 vs. 3.2 +/- 0.2 days, p < 0.001). After multivariate analysis adjusting for age, PIM probability of death, mean TISS-28 score during the first 48 h, post-operative admission, diagnosis of sepsis or trauma or malignancy, pre-transfusion Hb concentration, and RBC transfusion remained independently associated with mortality and morbidity. CONCLUSIONS: RBC transfusion in critically ill children is independently associated with increased mortality and prolonged duration of mechanical ventilation, prolonged infusion of vaso-active agents and prolonged PICU stay.