Safe prognostication following cardiac arrest: The role of the pharmacokinetics of fentanyl in patients treated with targeted temperature management.

BACKGROUND: Neurological prognostication following cardiac arrest (CA) is complex and sedative agents may significantly impair responses to clinical examination. This study investigates the elimination of fentanyl in patients treated with targeted temperature management (TTM). METHODS: We measured the blood concentration of fentanyl in 23 post-cardiac arrest patients treated with TTM following discontinuation of continuous infusion. Fentanyl was discontinued when the patients were rewarmed to a temperature of 36-36.5 °C and a blood sample taken 12 h later. Measured concentrations were compared with predicted concentrations using population pharmacokinetic parameters. Variables likely to prolong half-life were analysed using a multivariate regression model. RESULTS: We found a statistically significant difference between median measured and predicted concentrations (measured 0.93 µg/L [range 0.11-8.29 µg/L] vs. predicted 0.30 µg/L [range 0.16-0.59 µg/L]; p < 0.05). Univariate analysis identified a significant relationship between estimated fentanyl half-life and serum lactate concentrations (r = 0.45, p < 0.05). Multivariate linear regression identified two variables (SAPS score and genotype), which together were able to explain approximately 30 % of the variation in the population (adjusted R2 = 0.3177, p = 0.0194). No significant relationships were found between fentanyl half-life and patients' clinical or biochemical variables or co-administration of drugs metabolized by cytochrome p450. CONCLUSIONS: There is marked variation in the clearance of fentanyl following continuous infusion during TTM after CA which correlates with illness severity, lactate concentration and genetic polymorphisms of the cytochrome p450 liver enzymes. Sustained presence of fentanyl may influence response to neurological examination at 12 h post discontinuation in patients receiving the drug as an infusion as part of TTM.

Diagnostic echocardiography in an unstable intensive care patient.

UNLABELLED: A previously fit and well 57-year-old gentleman who had recently undergone a colonoscopy and biopsy of a polyp presented with a 4-day history of progressive breathlessness and abdominal discomfort. The day after admission, he became haemodynamically unstable, developed ischaemic legs and suffered a brief cardiac arrest. Blood tests demonstrated a coagulopathy and hypoglycaemia. Continued haemodynamic instability post-arrest and clinical findings of high right-sided heart pressures were investigated by bedside screening echocardiogram. This demonstrated a massive pericardial effusion causing tamponade of the right ventricle. Heavily blood stained pericardial fluid was drained, with marked improvement in haemodynamic stability. Retrospective review of the admission-electrocardiogram (ECG) and chest X-ray demonstrated electrical alternans and cardiac enlargement. The differential diagnosis included bowel malignancy causing a haemorrhagic metastatic pericardial effusion and a type A aortic dissection. Therefore a computerised tomography (CT) scan of chest, abdomen, pelvis and aorta was performed. This was negative for disseminated malignancy and showed a type B aortic dissection, but was inconclusive for a type A aortic dissection. A subsequent transoesophageal echocardiogram confirmed the diagnosis of type B dissection and ruled out a type A dissection. The histology of the colonic polyp was negative for malignancy, but it was subsequently discovered that the patient had metastatic adenocarcinoma from a primary lung cancer diagnosed from pleural fluid cytology. With hindsight the presenting clinical picture was of type B aortic dissection with concurrent but not directly related pericardial tamponade. LEARNING POINTS: Basic echocardiography skills are increasingly being used acutely by physicians' as part of resuscitative care in intensive care unit (ICU) patients.The availability of expert skills in transoesophageal echocardiography are essential in ICU, as demonstrated in this case, where it was needed for discriminating between sub types of aortic dissection.Cardiac tamponade is a clinical diagnosis, although the presence of electrical alternans on an ECG with associated tachycardia is highly suggestive of cardiac tamponade.

Manejo de la sialorrea en personas con enfermedad de Parkinson mediante terapia conductivo conductual y estimulación termo-táctil / Management of sialorrhea in people with Parkinson's disease through behavioral therapy and thermotactile stimulation

This study proposes a Speech Therapy treatment for individuals with sialorrhea (saliva production perceived by patient as excessive) as a consequence of Parkinson Disease (PD). Method: A prospective study in 18 individuals with PD diagnosis was taken and divided into two groups: A) received only Cognitive Behavioral Therapy (CBT) (swallowing process awareness), while B) received CBT plus Thermal Tactile Stimulation (TTS) (cold sensory stimulation to the pharyngeal anterior pillars and oral cavity). The intervention lasted 5 weeks. The purpose of this research was to prove the effectiveness of Speech Therapy in dealing with sialorrhea and to assess a significant difference between CBT and CBT plus TTS. A t-student parameter test and the Mann-Withney test were used. Resulted: The assessment by the Clinical Scale for Parkinson Sialorrhea (SCS-PD) prior to therapy was CBT group was 2.6 and 11.5 ± 9.4 ± 4.2 group difference was not statistically significant. After therapy was 3.5 ± 2.8 and 4.6 ± 3.5 both showed a statistically significant difference compared to baseline (p < 0.001), not having statistically significant difference between them. Conclusion: These tests showed that both treatments are effective to decrease sialorrhea perception in individuals with PD. Nevertheless, no statistical significant differences were noted between both treatments.

Introducción: Este estudio propone un tratamiento Fonoaudiológico para trabajar con personas que presentan sialorrea (producción de saliva que el paciente percibe como excesiva) producto de la Enfermedad de Parkinson (EP). Método: Dieciocho personas con diagnóstico de EP y sialorrea, las cuales se dividieron en dos grupos; A: recibió sólo Terapia Cognitivo Conductual (TCC) (concientización del proceso deglutorio), mientras el B: recibió TCC más Estimulación Termo Táctil (ETT) (se realiza estimulación sensorial con frío a los pilares faríngeos anteriores y cavidad oral), la intervención se realizó por 5 semanas. El objetivo de la presente investigación es evidenciar la efectividad de la terapia Fonoaudiológica en el abordaje de la sialorrea y evaluar si existe una diferencia significativa entre la TCC y la TCC más ETT. Se utilizó la prueba paramétrica t-student, y Test de Mann-Withney, se consideró significativo un p < 0,05. Resultados: La valoración mediante la Escala Clínica de la Sialorrea para Parkinson (SCS-PD) previo a la terapia en grupo con TCC 11,5 ± 2,6 y el grupo 9,4 ± 4,2 diferencia que no es estadísticamente significativa. Posterior a la terapia fue 3,5 ± 2,8 y 4,6 ± 3,5 ambos presentaron una diferencia estadísticamente significativa respecto a la basal (p < 0,001), no habiendo diferencia estadísticamente significativa entre ellas. Conclusión: Estas pruebas demostraron que ambos tratamientos son efectivos para disminuir la percepción de sialorrea en las personas con EP. Sin embargo, no se evidencian diferencias estadísticamente significativas entre ambos tratamientos.

Intraoperative pulmonary oedema in a child following systemic absorption of phenylephrine eyedrops.

Ophthalmic surgeons often apply phenylephrine topically to effect pupillary dilatation. We describe a paediatric patient in whom cardiac arrhythmias, severe hypertension and pulmonary oedema occurred following intraoperative ocular phenylephrine administration. We believe that systemic absorption of the drug was responsible and discuss ways in which this might be reduced when ocular phenylephrine is used in this context.

Lipid binding-induced conformational change in human apolipoprotein E. Evidence for two lipid-bound states on spherical particles.

Apolipoprotein (apo) E contains two structural domains, a 22-kDa (amino acids 1-191) N-terminal domain and a 10-kDa (amino acids 223-299) C-terminal domain. To better understand apoE-lipid interactions on lipoprotein surfaces, we determined the thermodynamic parameters for binding of apoE4 and its 22- and 10-kDa fragments to triolein-egg phosphatidylcholine emulsions using a centrifugation assay and titration calorimetry. In both large (120 nm) and small (35 nm) emulsion particles, the binding affinities decreased in the order 10-kDa fragment approximately 34-kDa intact apoE4 > 22-kDa fragment, whereas the maximal binding capacity of intact apoE4 was much larger than those of the 22- and 10-kDa fragments. These results suggest that at maximal binding, the binding behavior of intact apoE4 is different from that of each fragment and that the N-terminal domain of intact apoE4 does not contact lipid. Isothermal titration calorimetry measurements showed that apoE binding to emulsions was an exothermic process. Binding to large particles is enthalpically driven, and binding to small particles is entropically driven. At a low surface concentration of protein, the binding enthalpy of intact apoE4 (-69 kcal/mol) was approximately equal to the sum of the enthalpies for the 22- and 10-kDa fragments, indicating that both the 22- and 10-kDa fragments interact with lipids. In a saturated condition, however, the binding enthalpy of intact apoE4 (-39 kcal/mol) was less exothermic and rather similar to that of each fragment, supporting the hypothesis that only the C-terminal domain of intact apoE4 binds to lipid. We conclude that the N-terminal four-helix bundle can adopt either open or closed conformations, depending upon the surface concentration of emulsion-bound apoE.

Do patient information booklets increase perioperative anxiety?

Patient attitudes to medical information are changing. We audited patient attitudes to an information leaflet provided at the preadmission clinic as part of standard day-case protocol. The booklet is a simplified version of the booklet Anaesthesia and Anaesthetists--Information for Patients and Relatives published in London, UK, by the Association of Anaesthetists of Great Britain & Ireland. One hundred and three patients were surveyed before surgery over a 2-month period using an anonymous questionnaire. Of the 96% of patients who read the booklet provided, 99% found it helpful to some degree. Thirty-five per cent of patients found it worried them. Thirty-two per cent discussed the information with others but only 3% discussed the information provided with the anaesthetist. Although patients like to receive information about the process of anaesthesia, we must be careful that by providing it in an inappropriate form, e.g. as a leaflet, we do not increase their preoperative anxiety.