COACHRED: A protocol for the safe and timely incorporation of focused echocardiography into the rhythm check during cardiopulmonary resuscitation.

Focused echocardiography may be a useful tool in cardiopulmonary resuscitation for prognostication, to identify certain reversible causes of cardiac arrest, and to guide further management and procedures. Nonetheless, many clinicians have reservations regarding its widespread adoption due to evidence that it leads to prolonged interruption of cardiac compressions. Furthermore, the lack of a clear protocol for the inclusion of focused echocardiography into the rhythm check can lead to confusion in teams not familiar with incorporating the modality, as well as safety concerns for the echosonographer during delivery of a shock. We propose the protocol COACHRED to guide the use of focused echocardiography during rhythm check in a safe and timely manner. This approach incorporates the best strategies identified to date that minimise interruptions to chest compressions. We demonstrate that, in a simulation environment, it is achievable to incorporate focused echocardiography into the rhythm check while keeping the interruption to chest compressions within the timeframe prescribed by international guidelines.

Validation of emergency physician ultrasound in diagnosing hydronephrosis in ureteric colic.

OBJECTIVE: Patients presenting to the ED with obstructive nephropathies benefit from early detection of hydronephrosis. Out of hours radiological imaging is expensive and disruptive to arrange. Emergency physician ultrasound (EPU) could allow rapid diagnosis and disposition. If accurate it might avert the need for formal radiological imaging, exclude an obstruction and improve patient flow through the ED. METHODS: This was a prospective study of a convenience sample of all adult non-pregnant patients with presumed ureteric colic attending the ED with prior ethics committee approval. An emergency physician or registrar performed a focused ultrasound scan and were blinded to the patient's other management. A computerized tomography scan was also performed for all patients while in the ED or within 24 h of the EPU. The accuracy of EPU detection of hydronephrosis was determined; using computerized tomography scans reported by a senior radiologist as the 'gold-standard'. RESULTS: Sixty-three patients with suspected ureteric colic were enrolled of whom 57 completed both EPU and computerized tomography imaging. Forty-nine had confirmed nephrolithiasis by computerized tomography with 39 having evidence of hydronephrosis. Overall prevalence of hydronephrosis was 68% (95% confidence interval [CI] 56-79%); compared with computerized tomography, EPU had a sensitivity of 80% (95% CI 65-89%); specificity of 83% (95% CI 61-94%); positive predictive value of 91% (95% CI 75-98%) and negative predictive value of 65% (95% CI 43-83%). The overall accuracy was 81% (95% CI 69-89%). CONCLUSION: Although the accuracy of detection of hydronephrosis after focused training in EPU is encouraging, further experience and training might improve the accuracy of EPU and allow its use as a screening tool.

Lipoprotein-complexed C-reactive protein and the biphasic transmittance waveform in critically ill patients.

The 'biphasic transmittance waveform' (BTW) refers to a decrease in light transmittance that often occurs prior to clotting in coagulation assays of critically ill patient plasmas. It correlates with disseminated intravascular coagulation and mortality. The present work shows that the BTW is due to the rapid formation of a precipitate and a coincident change in turbidity in re-calcified plasma. The precipitate was isolated from patient plasma and contained lipids typical of very low density lipoprotein (VLDL), plus the proteins apolipoprotein B-100 and C-reactive protein (CRP). Precipitation also occurred in normal plasma supplemented with CRP. In addition, CRP precipitated with VLDL and intermediate density lipoprotein, but not low density lipoprotein or high density lipoprotein. The Kd value for the CRP/VLDL interaction is 340 nM. The IC50 value of Ca2+ for complex formation is 5.0 mM, and epsilon-aminocaproic acid inhibits the process. In 15 plasmas with the BTW from critically ill patients, CRP was highly elevated (77-398 microg/mL) and VLDL cholesterol ranged from 0.082 to 1.32 mM. The magnitude of the turbidity change on re-calcification correlated well with the calculated level of the CRP/VLDL complex. Thus, the Ca2+-dependent formation of a complex between CRP and VLDL accounts for the BTW.

Aberrant splicing and premature termination of transcription of the FVIII gene as a cause of severe canine hemophilia A: similarities with the intron 22 inversion mutation in human hemophilia.

We have identified the causative mutation in the hemophilia A dog colony at Queen's University, Canada and have observed a striking similarity with the intron 22 inversion found in approximately 45% of severely affected hemophilia A patients. The canine hemophilia A phenotype arises from aberrant splicing and premature termination of transcription of the FVIII gene, resulting in a polyadenylated transcript lacking exons distal to 22 and terminating with a novel sequence element (NSE). In dogs and other species including humans, this NSE is present in low copy number. One copy of these sequences in the canine genome is within intron 22 and reveals differences in the hybridization banding patterns between normal and hemophilic DNA, suggestive of a large genomic rearrangement. The mutation mechanism may not be uncommon, as identical mutant transcripts were isolated from two hemophilia A littermates that are unrelated to the Queen's colony and from hemophiliac dogs in the colony at Chapel Hill.

The utility of activated partial thromboplastin time (aPTT) clot waveform analysis in the investigation of hemophilia A patients with very low levels of factor VIII activity (FVIII:C).

The lower detection limit of the conventional one-stage aPTT based clotting assay for determining FVIII:C levels is generally 1.0-2.0 IU/dl. Consequently, it has been impossible to study the clinical significance of levels of FVIII:C less than 1.0 IU/dl. Using a photo-optical automated coagulation analyzer, the Organon Teknika MDA II, we have performed qualitative and quantitative aPTT waveform analysis and measured FVIII:C levels by automated one-stage aPTT clotting assay in 36 severely affected Hemophilia A patients. Qualitative waveform analysis showed clear evidence of individual differences in the waveform profile suggesting differing coagulant activity from patient to patient. The FVIII:C level was less than 0.2 IU/dl in 23 cases and levels of FVIII:C between 0.2 and 1.0 IU/dl could be discriminated in 13 patients. The FVIII:C level in these patients was closely correlated with the minimum value of the second derivative of the aPTT waveform (Min2). This is a measure of the acceleration of change in optical transmission at the initiation of coagulation. Furthermore, the correlation of the

Early identification of sepsis and mortality risks through simple, rapid clot-waveform analysis. Implications of lipoprotein-complexed C reactive protein formation.

OBJECTIVE: To determine if the rapid waveform profile of the activated partial thromboplastin time (aPTT) assay, which detects lipoprotein-complexed C reactive protein (LCCRP) formation, predicts sepsis and mortality in critically ill patients. DESIGN: Observational, cohort study. SETTING: General intensive therapy unit (ITU) of a tertiary care hospital. PATIENTS AND PARTICIPANTS: A total of 1187 consecutive patients admitted to the ITU. INTERVENTION: Activated partial thromboplastin time transmittance waveform analysis was performed within the first hour of admission to the ITU. The degree of change causing a biphasic waveform was quantified through the drop in light transmittance level. MEASUREMENTS AND RESULTS: Three hundred forty-six patients had a biphasic waveform on admission to the ITU with a mortality rate of 44% compared with 26% for those with normal waveforms. Logistic regression models showed direct correlation between the likelihood for sepsis and in-patient mortality with increasing waveform abnormalities. The mortality fraction was 0.3 with normal waveforms versus 0.6 when the light transmittance decreased by 30%. The odds ratio (OR) for mortality and sepsis were 4.5 and 11, respectively, from the most abnormal to normal aPTT waveforms. These were comparable with APACHE II scores and superior to those estimated by CRP for mortality (OR 2.3) / sepsis (OR 6.4) prediction. CONCLUSION: Waveform analysis within the first hour of ITU admission is a single, simple and rapid method of identifying the risks of mortality and sepsis. Its measure of LCCRP formation shows superior prediction over CRP alone and it warrants further assessment as a tool to triage and target prompt, appropriate treatment in the ITU.

Preclinical experiment of auxiliary partial orthotopic liver transplantation as a curative treatment for hemophilia.

The cause of hemophilia is deficiency of coagulation factor VIII production in the liver, which can be cured by liver transplantation. Because the hepatic function of hemophilia patients is quite normal except for production of factor VIII, auxiliary partial orthotopic liver transplantation (APOLT) is beneficial in that patient survival is secured by preserving native liver even in the event of graft loss. However, it is not known whether the graft of APOLT would be enough to cure hemophilia. We evaluated the efficacy and feasibility of APOLT for hemophilia in a canine hemophilia A model that we established. Partial left liver graft was taken from the normal donor (blood factor VIII activity > 60%). The graft was transplanted to the hemophilia beagle dog (blood factor VIII activity < 5%) after resection of the left lobe preserving native right lobe. Changes in time of blood factor VIII activity and liver function parameters were observed after APOLT. APOLT and perioperative hemostatic management were successfully performed. The blood factor VIII activity increased to 30% after APOLT, and was sustained at least 6 weeks throughout the observation period without symptoms of bleeding. The result demonstrated sustained production of factor VIII in the hemophilia recipient after APOLT. Transplantation of approximately one third of whole liver resulted in cure of hemophilia. In conclusion, it is suggested that APOLT would be feasible as a curative treatment of hemophilia A to improve quality of life of the patients.

An abnormal activated partial thromboplastin time clotting waveform is associated with high mortality and a procoagulant state.

We studied the associations of a biphasic waveform identified in 61 consecutive patients by activated partial thromboplastin times performed with an MDA 180 coagulation analyzer (bioMérieux Inc., Durham, NC, USA). The patients were encountered in a wide range of locations, including medical and surgical services, emergency and outpatient departments, and intensive care unit. The patients encountered also had a variety of clinical diagnoses. Of the patients, 42.6% were dead on follow-up evaluation at 3 months, and 67.2% had a clinical condition known to predispose to the development of disseminated intravascular coagulation (DIC). Sepsis was the most frequent associated condition and was present in 54% of the patients. Only 6 patients had overt DIC according to a standardized scoring system. However, D-dimer was elevated in 90% of patients, and antithrombin III and protein C levels decreased in 75.4% and 63.9%, respectively. The platelet count was decreased in 26%. Our results indicated that a biphasic waveform is associated with high mortality in general hospital patients and is frequently associated with sepsis. This waveform appears to be associated with a consumptive procoagulant state, which may represent early or nonovert DIC.

Biphasic transmittance waveform in the APTT coagulation assay is due to the formation of a Ca(++)-dependent complex of C-reactive protein with very-low-density lipoprotein and is a novel marker of impending disseminated intravascular coagulation.

A decrease in light transmittance before clot formation, manifesting as a biphasic waveform (BPW) pattern in coagulation assays, was previously correlated with the onset of disseminated intravascular coagulation (DIC). In this study of 1187 consecutive admissions to the intensive care unit, the degree of this change on admission predicts DIC better than D-dimer measurements. Additionally, the BPW preceded the time of DIC diagnosis by 18 hours, on average, in 56% (203 of 362) of DIC patients. The BPW is due to the rapid formation of a precipitate and coincident turbidity change on recalcification of plasma. The isolated precipitate contains very-low-density lipoprotein (VLDL) and C-reactive protein (CRP). The addition of CRP and Ca(++) to normal plasma also causes the precipitation of VLDL and IDL, but not LDL or HDL. The K(d) of the CRP/VLDL interaction is 340 nM, and the IC(50) for Ca(++) is 5.0 mM. In 15 plasmas with the BPW, CRP was highly elevated (77-398 microg/mL), and the concentration of isolated VLDL ranged from 0.082 to 1.32 mM (cholesterol). The turbidity change on recalcification correlates well with the calculated level of the CRP-VLDL complex. Clinically, the BPW better predicts for DIC than either CRP or triglyceride alone. The complex may have pathophysiological implications because CRP can be detected in the VLDL fraction from sera of patients with the BPW, and the VLDL fraction has enhanced prothrombinase surface activity. The complex has been designated lipoprotein complexed C-reactive protein.