Abel Wakai

Is human fracture hematoma inherently angiogenic

This study attempts to explain the cellular events characterizing the changes seen in the medullary callus adjacent to the interfragmentary hematoma during the early stages of fracture healing. It also shows that human fracture hematoma contains the angiogenic cytokine vascular endothelial growth factor and has the inherent capability to induce angiogenesis and thus promote revascularization during bone repair. Patients undergoing emergency surgery for isolated bony injury were studied. Raised circulating levels of vascular endothelial growth factor were seen in all injured patients, whereas the fracture hematoma contained significantly higher levels of vascular endothelial growth factor than did plasma from these injured patients. However, incubation of endothelial cells in fracture hematoma supernatant significantly inhibited the in vitro angiogenic parameters of endothelial cell proliferation and microtubule formation. These phenomena are dependent on a local biochemical milieu that does not support cytokinesis. The hematoma potassium concentration is cytotoxic to endothelial cells and osteoblasts. Subcutaneous transplantation of the fracture hematoma into a murine wound model resulted in new blood vessel formation after hematoma resorption. This angiogenic effect is mediated by the significant concentrations of vascular endothelial growth factor found in the hematoma. This study identifies an angiogenic cytokine involved in human fracture healing and shows that fracture hematoma is inherently angiogenic. The differences between the in vitro and in vivo findings may explain the phenomenon of interfragmentary hematoma organization and resorption that precedes fracture revascularization.

Pneumatic Tourniquets in Extremity Surgery

Pneumatic tourniquets maintain a relatively bloodless field during extremity surgery, minimize blood loss, aid identification of vital structures, and expedite the procedure. However, they may induce an ischemia‐reperfusion injury with potentially harmful local and systemic consequences. Modern pneumatic tourniquets are designed with mechanisms to regulate and maintain pressure. Routine maintenance helps ensure that these systems are working properly. The complications of tourniquet use include postoperative swelling, delay of recovery of muscle power, compression neurapraxia, wound hematoma with the potential for infection, vascular injury, tissue necrosis, and compartment syndrome. Systemic complications can also occur. The incidence of complications can be minimized by use of wider tourniquets, careful preoperative patient evaluation, and adherence to accepted principles of tourniquet use.

Tourniquet-induced systemic inflammatory response in extremity surgery.

BACKGROUND Tourniquet-induced reperfusion injury in animals produces significant systemic inflammatory effects. This study investigated whether a biologic response occurs in a clinically relevant model of tourniquet-induced reperfusion injury. METHODS Patients undergoing elective knee arthroscopy were prospectively randomized into controls (no tourniquet) and subjects (tourniquet-controlled). The effects of tourniquet-induced reperfusion on monocyte activation state, neutrophil activation state, and transendothelial migration (TEM) were studied. Changes in the cytokines implicated in reperfusion injury, tumor necrosis factor-alpha, interleukin (IL)-1beta, and IL-10 were also determined. RESULTS After 15 minutes of reperfusion, neutrophil and monocyte activation were significantly increased. Pretreatment of neutrophils with pooled subject (ischemia-primed) plasma significantly increased TEM. In contrast, TEM was not significantly altered by ischemia-primed plasma pretreatment of the endothelial monolayer. Significant elevation of tumor necrosis factor-alpha and IL-1beta were observed in subjects compared with controls after 15 minutes of reperfusion. There was no significant difference in serum IL-10 levels between the groups at all the time points studied. CONCLUSION These results indicate a transient neutrophil and monocyte activation after tourniquet-ischemia that translates into enhanced neutrophil transendothelial migration with potential for tissue injury.

The end of the line? The Visual Analogue Scale and Verbal Numerical Rating Scale as pain assessment tools in the emergency department

Objectives To compare the Visual Analogue Scale (VAS) and the Verbal Numerical Rating Scale (VNRS), in the assessment of acute pain in the emergency department (ED). Furthermore, to determine the influence of demographics on this agreement and practical limitations of the scales. Setting St Vincents University Hospital, Dublin; a 479-bed teaching hospital; annual ED census 36 000 adult patients. Methods A prospective observational study was conducted on ED patients with acute pain as a component of their presenting complaint. Eligible patients scored their pain on both VAS and VNRS within 1 hour of arrival. They rescored their pain every 30 minutes for 2 hours using both scales. The primary outcome measure was agreement between VAS and VNRS. Secondary outcomes were ease of pain scale use and effect of patient demographics on pain scores. Agreement between scores was evaluated using the Bland-Altman method. Results 123 patients were included (median age 35; 43.9% male). There was a strong correlation between VAS and VNRS (rs=0.93). However, there was not perfect agreement between the two scales. Patient age (older age, p<0.005, t=−4.448), gender (female sex, p<0.005, t=4.903) and educational level attained (third level education, p<0.005, t=5.575) had a statistically significant influence on the agreement between VAS and VNRS. There was a preference for VNRS in those patients who expressed a preference for one pain scale over the other. Conclusions VAS and VNRS are not interchangeable in assessing an individual patients pain over time in the ED setting. VNRS has practical advantages over VAS in this setting.

Development of key performance indicators for emergency departments in Ireland using an electronic modified-Delphi consensus approach.

Objective The objective of this study was to develop a consensus among emergency medicine (EM) specialists working in Ireland for emergency department (ED) key performance indicators (KPIs). Methods The method employed was a three-round electronic modified-Delphi process. An online questionnaire with 54 potential KPIs was set up for round 1 of the Delphi process. The Delphi panel consisted of all registered EM specialists in Ireland. Each indicator on the questionnaire was rated using a five-point Likert-type rating scale. Agreement was defined as at least 70% of the responders rating an indicator as ‘agree’ or ‘strongly agree’ on the rating scale. Data were analysed using standard descriptive statistics. Data were also analysed as the mean of the Likert rating with 95% confidence intervals (95% CIs). Sensitivity of the ratings was examined for robustness by bootstrapping the original sample. Statistical analyses were carried out using SPSS version 16.0. Results The response rates in rounds 1, 2 and 3 were 86, 88 and 88%, respectively. Ninety-seven potential indicators reached agreement after the three rounds. In the context of the Donabedian structure–process–outcome framework of performance indicators, 41 (42%) of the agreed indicators were structure indicators, 52 (54%) were process indicators and four (4%) were outcome indicators. Overall, the top-three highest rated indicators were: presence of a dedicated ED clinical information system (4.7; 95% CI 4.6–4.9), ED compliance with minimum design standards (4.7; 95% CI 4.5–4.8) and time from ED arrival to first ECG in suspected cardiac chest pain (4.7; 95% CI 4.5–4.9). The top-three highest rated indicators specific to clinical care of children in EDs were: time to administration of antibiotics in children with suspected bacterial meningitis (4.6; 95% CI 4.5–4.8), separate area available within EDs (seeing both adults and children) to assess children (4.4; 95% CI 4.2–4.6) and time to administration of analgesia in children with forearm fractures (4.4; 95% CI 4.2–4.7). Conclusion Employing a Delphi consensus process, it was possible to reach a consensus among EM specialists in Ireland on a suite of 97 KPIs for EDs.

A qualitative study of the barriers to prehospital management of acute pain in children

Introduction Effective pain management in the prehospital setting is gaining momentum as a potential key performance indicator by many emergency medical service systems, but historically has been shown to be inadequate, particularly in the paediatric population. This study aimed to identify the barriers, as perceived by a national cohort of advanced paramedics (APs), to achieving optimal prehospital management of acute pain in children. Methods A qualitative approach was employed to capture data through two focus group interviews. Sixteen APs were invited to participate in this study. Both focus groups were audio recorded, transcribed and analysed using Attride–Stirlings framework for thematic network analysis. Results The global theme ‘Understanding Barriers to the Prehospital Management of Acute Pain in Children’ emerged from three organising themes as follows: AP education and training; current clinical practice guidelines for paediatric pain management; realities of prehospital practice. Limited exposure to children in the prehospital setting, difficulty assessing pain intensity in small children, and challenges in administering oral or inhaled analgesic agents to distressed and uncooperative children were highlighted by participants. Short transfer times to the emergency department, and a ‘medical’ cause of pain were also implicated as examples of when children are less likely to receive analgesia from practitioners. Conclusions The pathway to improving care must include an emphasis on improvements in practitioner education and training, offering alternatives to assessing pain in preverbal children, exploring the intranasal route of drug delivery in managing acute severe pain, and robustly developed evidence-based guidelines that are practitioner friendly and patient-focused.

Risk factors for nonpurulent leg cellulitis: a systematic review and meta-analysis

Nonpurulent cellulitis is an acute bacterial infection of the dermal and subdermal tissues that is not associated with purulent drainage, discharge or abscess. The objectives of this systematic review and meta‐analysis were to identify and appraise all controlled observational studies that have examined risk factors for the development of nonpurulent cellulitis of the leg (NPLC). A systematic literature search of electronic databases and grey literature sources was performed in July 2015. The Newcastle–Ottawa Scale (NOS) was used to assess methodological quality of included studies. Of 3059 potentially eligible studies retrieved and screened, six case–control studies were included. An increased risk of developing NPLC was associated with previous cellulitis [odds ratio (OR) 40·3, 95% confidence interval (CI) 22·6–72·0], wound (OR 19·1, 95% CI 9·1–40·0), current leg ulcers (OR 13·7, 95% CI 7·9–23·6), lymphoedema/chronic leg oedema (OR 6·8, 95% CI 3·5–13·3), excoriating skin diseases (OR 4·4, 95% CI 2·7–7·1), tinea pedis (OR 3·2, 95% CI 1·9–5·3) and body mass index > 30 kg m−2 (OR 2·4, 95% CI 1·4–4·0). Diabetes, smoking and alcohol consumption were not associated with NPLC. Although diabetics may have been underrepresented in the included studies, local risk factors appear to play a more significant role in the development of NPLC than do systemic risk factors. Clinicians should consider the treatment of modifiable risk factors including leg oedema, wounds, ulcers, areas of skin breakdown and toe‐web intertrigo while administering antibiotic treatment for NPLC.

Intranasal fentanyl versus intravenous morphine in the emergency department treatment of severe painful sickle cell crises in children: Study protocol for a randomised controlled trial

BackgroundChildren with sickle cell disease (SCD) frequently and unpredictably present to the emergency department (ED) with pain. The painful event is the hallmark acute clinical manifestation of SCD, characterised by sudden onset and is usually bony in origin. This study aims to establish if 1.5mcg/kg of intranasal fentanyl (INF; administered via a Mucosal Atomiser Device, MAD™) is non-inferior to intravenous morphine 0.1 mg/kg in severe SCD-associated pain.Methods/designThis study is a randomised,double-blind, double-dummy active control trial of children (weighing more than 10 kg) between 1 year and 21 years of age with severe painful sickle cell crisis. Severe pain is defined as rated seven or greater on a 0 to 10 age-appropriate numeric pain scale or equivalent. The trial will be conducted in a single tertiary urban paediatric ED in Dublin, Ireland. Each patient will receive a single active agent and a single placebo via the intravenous and intranasal routes. All clinical and research staff, patients and parents will be blinded to the treatment allocation. The primary endpoint is severity of pain scored at 10 min from administration of the study medications. Secondary endpoints include pain severity measured at 0, 5, 15, 20, 30, 60 and 120 min after the administration of analgesia, proportion of patients requiring rescue analgesia and incidence of adverse events. The trial ends at 120 min after the administration of the study drugs. A clinically meaningful difference in validated pain scores has been defined as 13 mm. Setting the permitted threshold to 50% of this limit (6 mm) and assuming both treatments are on average equal, a sample size of 30 patients (15 per group) will provide at least 80% power to demonstrate that INF is non-inferior to IV morphine with a level of significance of 0.05.DiscussionThis clinical trial will inform of the role of INF 1.5mcg/kg via MAD in the acute treatment of severe painful sickle cell crisis in children in the ED setting.Trial registrationCurrent Controlled Trials ISRCTN67469672 and EudraCT no. 2011-005161-20

Single dose oral dexamethasone versus multi-dose prednisolone in the treatment of acute exacerbations of asthma in children who attend the emergency department: study protocol for a randomized controlled trial

BackgroundAsthma is a major cause of pediatric morbidity and mortality. In acute exacerbations of asthma, corticosteroids reduce relapses, subsequent hospital admission and the need for ß2-agonist therapy. Prednisolone is relatively short-acting with a half-life of 12 to 36 hours, thereby requiring daily dosing. Prolonged treatment course, vomiting and a bitter taste may reduce patient compliance with prednisolone. Dexamethasone is a long-acting corticosteroid with a half-life of 36 to 72 hours. It is used frequently in children with croup and bacterial meningitis, and is well absorbed orally. The purpose of this trial is to examine whether a single dose of oral dexamethasone (0.3 mg/kg) is clinically non-inferior to prednisolone (1 mg/kg/day for three days) in the treatment of exacerbations of asthma in children who attend the Emergency Department.Methods/designThis is a randomized, non-inferiority, open-label clinical trial. After informed consent with or without assent, patients will be randomized to either oral dexamethasone 0.3 mg/kg stat or prednisolone 1 mg/kg/day for three days. The primary outcome measure is the comparison between the Pediatric Respiratory Assessment Measure (PRAM) across both groups on Day 4. The PRAM score, a validated, responsive and reliable tool to determine asthma severity in children aged 2 to 16 years, will be performed by a clinician blinded to treatment allocation. Secondary outcomes include relapse, hospital admission and requirement for further steroid therapy. Data will be analyzed on an intention-to-treat and a per protocol basis. With a sample size of 232 subjects (105 in each group with an estimated 10% loss to follow-up), we will be able to reject the null hypothesis - that the population means of the experimental and control groups are equal with a probability (power) of 0.9. The Type I error probability associated with this test (of the null hypothesis) is 0.05.DiscussionThis clinical trial may provide evidence that a shorter steroid course using dexamethasone can be used in the treatment of acute pediatric asthma, thus eliminating the issue of compliance to treatment.RegistrationISRCTN26944158 and EudraCT Number 2010-022001-18

Intranasal fentanyl for the prehospital management of acute pain in children.

Introduction Acute pain is the most common symptom in the emergency setting and its optimal management continues to challenge prehospital emergency care practitioners, particularly in the paediatric population. Difficulty in establishing vascular access and fear of opiate administration to small children are recognized reasons for oligoanalgesia. Intranasal fentanyl (INF) has been shown to be as safe and effective as intravenous morphine in the treatment of severe pain in children in the Emergency Department setting. Aim This study aimed to describe the clinical efficacy and safety of INF when administered by advanced paramedics in the prehospital treatment of acute severe pain in children. Methods A 1-year prospective cross-sectional study was carried out of children (>1 year, <16 years) who received INF as part of the prehospital treatment of acute pain by the statutory national emergency medical services in Ireland. Results Ninety-four children were included in the final analysis [median age 11 years (interquartile range 7–13)]; 53% were males and trauma was implicated in 86% of cases. A clinically effective reduction in the pain score was found in 78 children [83% (95% confidence interval: 74–89%)]. The median initial pain rating score was 10. Pain assessment at 10 min after INF administration indicated a median pain rating of 5 (interquartile range 2–7). No patient developed an adverse event as a result of INF. Discussion INF at a dose of 1.5 µg/kg appears to be a safe and effective analgesic in the prehospital management of acute severe pain in children and may be an attractive alternative to both oral and intravenous opiates.