The sensitivity and specificity of rotational thromboelastometry (ROTEM) to detect coagulopathy during moderate and severe postpartum haemorrhage: a prospective observational study.

INTRODUCTION: Point-of-care viscoelastic haemostatic assays such as rotational thromboelastometry (including ROTEM and TEG) have been used in the management of postpartum haemorrhage (PPH). This study compared results obtained from the automated ROTEM Sigma with laboratory tests of coagulation and platelet count during PPH. METHODS: A prospective observational cohort study recruited women with PPH ≥1000 mL (or clinical concern of bleeding). The Fibtem A5, Extem CT and Pltem (Extem A5 - Fibtem A5) results were compared with laboratory tests of fibrinogen, prothrombin time (PT), activated partial thromboplastin time (APTT) and platelet count. RESULTS: 521 women were recruited, including 274/277 (98.9%) of women with PPH ≥1500 mL. Fibtem A5 results were matched with laboratory fibrinogen in 552/644 (85.7%) samples. The incidence of abnormal laboratory results was low: fibrinogen ≤2 g/L 23/464 (5.0%), PT or APTT >1.5 × midpoint of reference range 4/464 (0.9%), and platelet count <75 × 109/L 11/477 (2.3%). Area-under-the-receiver operator characteristic curve for Fibtem A5 to detect fibrinogen ≤2 g/L was 0.96 (95% Confidence Interval (CI) 0.94 to 0.98, P<0.001), with sensitivity and specificity of Fibtem A5 ≤11 mm to detect fibrinogen ≤2 g/L of 0.76 and 0.96. Prolonged Extem CT results improved after treatment of hypofibrinogenaemia alone. Intervention points for platelet and fresh frozen plasma (FFP) transfusion based on ROTEM Sigma parameters could not be established. CONCLUSION: During PPH (≥1000 mL or cases of clinical concern about bleeding), ROTEM Sigma Fibtem A5 can detect fibrinogen ≤2 g/L and guide targeted fibrinogen replacement. Laboratory results should continue to be used to guide platelet and FFP transfusion.

Utility of viscoelastography with TEG 6s to direct management of haemostasis during obstetric haemorrhage: a prospective observational study.

BACKGROUND: The TEG 6s is an automated cartridge-based device with limited description of use in obstetric haemorrhage. The aim of this analysis was to describe the utility of TEG 6s in identifying abnormal laboratory results of coagulation and platelet count, and inform an interventional treatment algorithm for postpartum haemorrhage. METHODS: A prospective observational cohort study of 521 women with moderate to severe obstetric haemorrhage (>1000 mL blood loss), including 372 women with at least one TEG 6s test. A non-pregnant control group was used for reference. TEG 6s test parameters Citrated Functional Fibrinogen (CFF), Citrated Kaolin TEG (CK) and Citrated Rapid TEG (CRT) were compared with paired laboratory tests of fibrinogen, PT/aPTT and platelet count, obtained during haemorrhage. RESULTS: Among 456 TEG 6s tests, 389 were matched with laboratory coagulation results. The receiver operator characteristic area-under-the-curve (95% CI) for CFF amplitude by 10 min to detect Clauss fibrinogen ≤2 g/L was 0.95 (0.91 to 0.99) (P<0.0001, sensitivity 0.74 and specificity 0.97 at ≤17 mm). False positives had median (IQR) Clauss fibrinogen of 2.4 (2.3-2.7) g/L. The CK-R time had some utility for detecting prolonged PT/aPTT, however a threshold for fresh frozen plasma transfusion was not established. A CRT maximum amplitude <57 mm, when CFF was ≥15 mm, identified four of eight samples with platelet count <75 × 109/L. CONCLUSION: The TEG 6s CFF can be used to identify low fibrinogen during obstetric haemorrhage. A value to identify transfusion thresholds for PT/aPTT and platelets was not established, and laboratory results should continue to be used.

When does obstetric coagulopathy occur and how do I manage it?

Anticipating obstetric coagulopathy is important when obstetric anaesthetists are involved in the clinical management of women with postpartum haemorrhage. Although the incidence of coagulopathy in women with postpartum haemorrhage is low, significant hypofibrinogenaemia is associated with major haemorrhage-related morbidity and thus early identification and treatment is essential to improve outcomes. Point-of-care viscoelastic haemostatic assays, including thromboelastography and rotational thromboelastometry, provide granular information about alterations in clot formation and hypofibrinogenaemia, allow near-patient interpretation of coagulopathy, and can guide goal-directed treatment. If these assays are not available, anaesthetists should closely monitor the maternal coagulation profile with standard laboratory testing during the active phase of postpartum bleeding in order to rule coagulopathy 'in or out', decide if pro-haemostatic therapies are indicated, and assess the response to haemostatic support.

Blister beetle dermatitis caused by cantharidin in South Sudan in Op TRENTON: a case series.

Cantharidin-producing blister beetles are found worldwide. The pathognomonic feature of their toxin is a blistering dermatitis that presents an environmental health hazard. Cutaneous exposure to cantharidin can produce blistering dermatitis, most commonly seen on exposed skin, in the Bentiu region of South Sudan. This should be treated with appropriate cleaning, debridement and regular dressing changes to cope with extensive initial exudate. The best dressing combinations found were initial treatment with povidone-iodine and hydrocolloid, followed by hydrocolloid only. Hydrocolloid dressings were found to be the most effective at staying in place with South Sudan's high humidity. Prevention strategies should include covering exposed skin, wearing wide-brimmed hats, neck scarves and enclosed footwear, and avoidance of working under white light. Medical personnel should engage with the chain of command to include appropriate force protection education within the arrivals brief.

Phosgene use in World War 1 and early evaluations of pathophysiology.

World War 1 ended 100 years ago. The aftermath included the consolidation of significant advances in medical care of casualties. Some of these advances were made in the care of chemical casualties, in particular the mechanisms of toxicity and treatment of phosgene exposure. Phosgene, or carbonyl chloride, is an extremely poisonous vapour that was used to devastating effect during World War 1. Observations made of acutely poisoned casualties formed the basis of much research in the early post-World War 1 era. Some extremely elegant experiments, some at the nascent Porton Down research facility, further evaluated the toxin and defences against it. Researchers drew on knowledge that was later forgotten and has since been relearnt later in the 20th century and made many correct assumptions. Their work is the bedrock of our understanding of phosgene toxicity that survives to this day. The horrors of chemical warfare prompted the Geneva Protocol of 1925, prohibiting the use of chemical agents in warfare, and chemical warfare on this scale has not been repeated. The ease with which phosgene can be synthesised requires healthcare providers to be familiar with its effects.

Enhanced case management can be delivered for patients with EVD in Africa: Experience from a UK military Ebola treatment centre in Sierra Leone.

BACKGROUND: Limited data exist describing supportive care management, laboratory abnormalities and outcomes in patients with Ebola virus disease (EVD) in West Africa. We report data which constitute the first description of the provision of enhanced EVD case management protocols in a West African setting. METHODS: Demographic, clinical and laboratory data were collected by retrospective review of clinical and laboratory records of patients with confirmed EVD admitted between 5 November 2014 and 30 June 2015. RESULTS: A total of 44 EVD patients were admitted (median age 37 years (range 17-63), 32/44 healthcare workers), and excluding those evacuated, the case fatality rate was 49% (95% CI 33%-65%). No pregnant women were admitted. At admission 9/44 had stage 1 disease (fever and constitutional symptoms only), 12/44 had stage 2 disease (presence of diarrhoea and/or vomiting) and 23/44 had stage 3 disease (presence of diarrhoea and/or vomiting with organ failure), with case fatality rates of 11% (95% CI 1%-58%), 27% (95% CI 6%-61%), and 70% (95% CI 47%-87%) respectively (p = 0.009). Haemorrhage occurred in 17/41 (41%) patients. The majority (21/40) of patients had hypokalaemia with hyperkalaemia occurring in 12/40 patients. Acute kidney injury (AKI) occurred in 20/40 patients, with 14/20 (70%, 95% CI 46%-88%) dying, compared to 5/20 (25%, 95% CI 9%-49%) dying who did not have AKI (p = 0.01). Ebola virus (EBOV) PCR cycle threshold value at baseline was mean 20.3 (SD 4.3) in fatal cases and 24.8 (SD 5.5) in survivors (p = 0.007). Mean national early warning score (NEWS) at admission was 5.5 (SD 4.4) in fatal cases and 3.0 (SD 1.9) in survivors (p = 0.02). Central venous catheters were placed in 37/41 patients and intravenous fluid administered to 40/41 patients (median duration of 5 days). Faecal management systems were inserted in 21/41 patients, urinary catheters placed in 27/41 and blood component therapy administered to 20/41 patients. CONCLUSIONS: EVD is commonly associated life-threatening electrolyte imbalance and organ dysfunction. We believe that the enhanced levels of protocolized care, scale and range of medical interventions we report, offer a blueprint for the future management of EVD in resource-limited settings.

Safety and feasibility of a strategy of early central venous catheter insertion in a deployed UK military Ebola virus disease treatment unit.

PURPOSE: Early central venous catheter (CVC) insertion in Ebola virus disease (EVD) is a novel approach and has not previously been described. This report delineates the safety, feasibility and clinical implications of early CVC insertion as the optimum means of vascular access in patients with EVD, in the setting of a deployed military Ebola virus disease treatment unit in Sierra Leone. METHODS: In the gastrointestinal phase of EVD, a 7-French 20-cm triple-lumen CVC was inserted using aseptic technique. Data were collected prospectively on all cases to include baseline and subsequent blood test variables, insertion site and technique, and complications associated with CVC placement. RESULTS: Twenty-three patients underwent CVC insertion as follows: subclavian, 21 (88 %); internal jugular, 2 (8 %); axillary, 1 (4 %). The mean duration of CVC placement was 5 days. There were no significant procedure-related adverse events. Despite coagulopathy being present in 75 % of cases, CVC insertion was safe, and there was only 1 case of significant catheter site bleeding. A total of 152 needle venepunctures were avoided owing to the presence of a CVC, a mean of 7 (±3.8) per case over the average stay. CONCLUSION: The early use of CVCs in Ebola virus disease is safe, effective and facilitates patient care. It should be considered a feasible additional route of venous access, where physician expertise and resources allow.

Toxicology and military anaesthesia.

The combination of trauma and poisoning is a situation likely to be faced by a deployed force at some point. This article provides practical advice on how to deal with poisoned patients without deviating from the concept of damage control resuscitation. The constraints of limited diagnostics, both at the scene and clinically, and lack of antidotal therapy are fundamental to the practice of clinical toxicology. Some of the specific therapies such as atropine and oximes were not evaluated prior to their introduction and there are few randomised controlled trials of poisoned patients. Most of the diagnoses will be made on clinical grounds and most of the therapy will be supportive; this article aims to reassure military anaesthetists in the process of dealing with the poisoned trauma patient.

Enteral drugs given through a central venous catheter.

A 74-year-old lady was given verapamil oral solution and a diclofenac dispersible tablet through her subclavian central venous catheter instead of her nasogastric tube five days after major head and neck surgery. The ensuing respiratory arrest resulting from profound ventilation-perfusion mismatch was made harder to manage by her potentially difficult airway. Information about the management of enteral drugs inadvertently given intravenously is sparse, and this sort of misrouting error is likely to be underreported. This case highlights the ease with which enteral preparations can be given by the wrong route.

Global analysis of transcription kinetics during competence development in Streptococcus pneumoniae using high density DNA arrays.

The kinetics of global changes in transcription patterns during competence development in Streptococcus pneumoniae was analysed with high-density arrays. Four thousand three hundred and one clones of a S. pneumoniae library, covering almost the entire genome, were amplified by PCR and gridded at high density onto nylon membranes. Competence was induced by the addition of CSP (competence stimulating peptide) to S. pneumoniae cultures grown to the early exponential phase. RNA was extracted from samples at 5 min intervals (for a period of 30 min) after the addition of CSP. Radiolabelled cDNA was generated from isolated total RNA by random priming and the probes were hybridized to identical high density arrays. Genes whose transcription was induced or repressed during competence were identified. Most of the genes previously known to be competence induced were detected together with several novel genes that all displayed the characteristic transient kinetics of competence-induced genes. Among the newly identified genes many have suggested functions compatible with roles in genetic transformation. Some of them may represent new members of the early or late competence regulons showing competence specific consensus sequences in their promoter regions. Northern experiments and mutational analysis were used to confirm some of the results.

Quantitative polymerase chain reaction to predict occurrence of symptomatic cytomegalovirus infection and assess response to ganciclovir therapy in renal transplant recipients.

Cytomegalovirus (CMV) DNA levels were measured by quantitative-competitive polymerase chain reaction (PCR) in weekly leukocyte samples from 50 renal transplant recipients, including 23 with symptomatic and 27 with asymptomatic CMV infection. Peak and week 4 CMV DNA levels were higher in symptomatic subjects (P = .07 and .02, respectively). In a logistic regression model, the logarithm of the week 4 level independently predicted symptomatic infection (odds ratio, 1.78 for a 1 log10 increase; 95% confidence interval, 1.14-2.78; P = .01). All subjects whose week 4 level exceeded 1000 copies/100,000 leukocytes developed symptoms. In subjects with adequate samples for analysis, CMV levels declined exponentially with ganciclovir treatment, with an average half-life of 3.3 days. Levels exceeding 10,000 copies were associated with prolonged time to clearing of CMV DNA. Potential clinical applications of quantitative CMV PCR include predicting occurrence of symptomatic first episodes after transplantation and individualizing duration of antiviral therapy.

Effects of storage temperature and time on qualitative and quantitative detection of cytomegalovirus in blood specimens by shell vial culture and PCR.

Cytomegalovirus (CMV) infectious titers and DNA levels were determined by quantitative shell vial culture and quantitative-competitive PCR with blood samples from 10 renal transplant recipients with active CMV infection. Blood samples were stored at either room temperature or 4 degrees C and were processed at intervals of 0, 6, 24, 48, and 72 h. All samples were culture and PCR positive at baseline. Whereas the sensitivity of shell vial culture progressively declined, with only 55% positive at 24 h and 10% positive at 48 h, all samples remained PCR positive at all time points. Furthermore, the infectious titer diminished by 83 to 91% by 24 h compared to that at baseline (P < 0.0001), but quantitative DNA levels did not decline over time. Storage temperature had no significant effect on either infectious titer or DNA levels.

Multiplex PCR for diagnosis of AIDS-related central nervous system lymphoma and toxoplasmosis.

A nested multiplex PCR assay was designed for the simultaneous detection of Epstein-Barr virus and Toxoplasma gondii DNA from the cerebrospinal fluid of AIDS patients. T. gondii DNA was detected in 8 of 8 patients with Toxoplasma encephalitis and in 0 of 6 patients without toxoplasmosis, and Epstein-Barr virus DNA was found in 9 of 14 patients with central nervous system lymphoma and in 2 of 38 patients without disease.