Consensus guidelines on analgesia and sedation in dying intensive care unit patients

Background

Intensivists must provide enough analgesia and sedation to ensure dying patients receive good palliative care. However, if it is perceived that too much is given, they risk prosecution for committing euthanasia. The goal of this study is to develop consensus guidelines on analgesia and sedation in dying intensive care unit patients that help distinguish palliative care from euthanasia.

Methods

Using the Delphi technique, panelists rated levels of agreement with statements describing how analgesics and sedatives should be given to dying ICU patients and how palliative care should be distinguished from euthanasia. Participants were drawn from 3 panels: 1) Canadian Academic Adult Intensive Care Fellowship program directors and Intensive Care division chiefs (N = 9); 2) Deputy chief provincial coroners (N = 5); 3) Validation panel of Intensivists attending the Canadian Critical Care Trials Group meeting (N = 12).

Results

After three Delphi rounds, consensus was achieved on 16 statements encompassing the role of palliative care in the intensive care unit, the management of pain and suffering, current areas of controversy, and ways of improving palliative care in the ICU.

Conclusion

Consensus guidelines were developed to guide the administration of analgesics and sedatives to dying ICU patients and to help distinguish palliative care from euthanasia.     

Cardiorespiratory responses to exercise in acute hypoxia, hyperoxia and normoxia

There is a prevailing hypothesis that an acute change in the fraction of oxygen in inspired air (F _IO₂) has no effect on maximal cardiac output ( ), although maximal oxygen uptake ( ) and exercise performance do vary along with F _IO₂. We tested this hypothesis in six endurance athletes during progressive cycle ergometer exercise in conditions of hypoxia (F _IO₂=0.150), normoxia (F _IO₂=0.209) and hyperoxia (F _IO₂=0.320). As expected, decreased in hypoxia [mean (SD) 3.58 (0.45) l·min^–1, P<0.05] and increased in hyperoxia [5.17 (0.34) l·min^–1, P<0.05] in comparison with normoxia [4.55 (0.32) l·min^–1]. Similarly, maximal power ( ) decreased in hypoxia [334 (41) W, P<0.05] and tended to increase in hyperoxia [404 (58) W] in comparison with normoxia [383 (46) W]. Contrary to the hypothesis, was 25.99 (3.37) l·min^–1 in hypoxia (P<0.05 compared to normoxia and hyperoxia), 28.51 (2.36) l·min^–1 in normoxia and 30.13 (2.06) l·min^–1 in hyperoxia. Our results can be interpreted to indicate that (1) the reduction in in acute hypoxia is explained both by the narrowing of the arterio-venous oxygen difference and reduced , (2) reduced in acute hypoxia may be beneficial by preventing a further decrease in pulmonary and peripheral oxygen diffusion, and (3) reduced and in acute hypoxia may be the result rather than the cause of the reduced and skeletal muscle recruitment, thus supporting the existence of a central governor. Electronic Publication     

Effect of Alkyl Groups of Latent Cationic Catalysts on Cure and Dynamic Mechanical Behaviors of Epoxy Resins

Summary: The latent thermal cationic initiators, benzyl‐2,5‐dimethylpyrazinium hexafluoroantimonate (BDPH) and benzyl‐2‐ethylpyrazinium hexafluoroantimonate (BEPH), were synthesized to investigate the effect of substituted alkyl groups on cure and dynamic mechanical behaviors of difunctional epoxy system. The cure temperature and activation energy of the diglycidyl ether of bisphenol A (DGEBA)/BDPH were higher than those of the DGEBA/BEPH, resulting from the steric hindrance of the substituted groups. The cross‐linking density of the DGEBA/BDPH was higher than that of the DGEBA/BEPH, whereas the T_g's of both specimens are similar. This may be explained by the free volume and the intermolecular hydrogen bonding induced by the hydrogen of the substituted methyl groups. Consequently, the position and number of the substituted groups of the latent thermal initiator were very important in the control of the latent thermal and dynamic mechanical behaviors of the epoxy resin.

Dynamic DSC curves of DGEBA cured by each initiator.     

Apolipoprotein(a) phenotypes are reliable biomarkers for familial aggregation of coronary heart disease

Lipoprotein(a) [Lp(a)] is an atherogenic and prothrombotic molecule formed by the covalent binding of the highly polymorphic apolipoprotein(a) [apo(a)] to apoprotein B-100 of LDL. High Lp(a) concentrations are a recognized genetic risk factor for coronary heart disease (CHD) and have been shown to be related with a familial clustering of ischemic cardiac events. Nevertheless, the association between apolipoprotein(a) isoforms and a positive familial history of CHD has received far less attention. In this report, we explored the distribution of apo(a) phenotypes in 127 CHD subjects with a family history of coronary events and in 92 CHD patients without such a history. Twenty-two apo(a) isoforms were detected by a high-resolution immunoblotting method. In univariate analysis, the percentage of subjects with at least one small sized apo(a) isoform was significantly higher in CHD patients with a positive family history than in those without (P<0.01). Multivariate analysis showed that apo(a) isoforms of low molecular weight were the best predictors of familial aggregation of cardiac ischemia. We conclude that apo(a) size polymorphism is strongly associated with a familial history of CHD and is more efficient than Lp(a) plasma concentrations in predicting the familial clustering of coronary disease. When detected by high-resolution techniques, apo(a) phenotypes are objective laboratory markers that can substitute for a knowledge of a positive family history of CHD and should be used, together with Lp(a) levels, to better assess the familial predisposition to coronary events.     

Psychopathological traits and 5-HT2A receptor promoter polymorphism (-1438 G/A) in patients suffering from Anorexia Nervosa and Bulimia Nervosa

Various studies have evaluated the possible role of the -1438G/A polymorphism within the 5-HT2A receptor gene in the susceptibility to Eating Disorders (EDs). One hundred and forty-eight ED patients (EDp) and 89 control subjects were interviewed by means of the Eating Disorder Examination (EDE) and analyzed for distribution of the -1438G/A polymorphism. Patients with the AA genotype suffering from Anorexia Nervosa and Bulimia Nervosa showed higher Weight and Shape Concern (P = 0.003 and P = 0.010, respectively) scores and greater overall severity of the ED psychopathology (EDE total score) (P = 0.012). The obtained preliminary data suggest the use of dimensional psychopathological measures in ED genetic studies.     

Dissecting karyotypic patterns in renal cell carcinoma: an analysis of the accumulated cytogenetic data

Molecular cytogenetic analysis frequently shows human papillomavirus (HPV) integration near translocation breakpoints in cervical cancer cells. We have recently described a cluster of HPV18 integrations in the distal end of the common fragile site FRA8C at 8q24 in primary cervical carcinoma samples. Chromosome band 8q24 contains the MYC gene (alias c-MYC), FRA8C, and FRA8D. The MYC gene is frequently deregulated--usually by translocation or amplification--in various tumor types. In the present study, we performed a molecular cytogenetic analysis of HPV18 integration patterns and the 8q24 translocation in a primary cervical carcinoma and in HeLa cells using combined binary ratio-fluorescence in situ hybridization. Our aim was to determine how the chromosomal breaks involved in these events relate physically to the MYC gene; whether they map to the FRA8C site, the FRA8D site, or both; and how they correlate with the occurrence of DNA flexibility domains. The 8q24 translocation breakpoints mapped between stretches of integrated HPV18 sequences in the distal end of FRA8C. This region contained DNA helix flexibility clusters, several of which mapped in the vicinity of HPV integration sites and translocation breakpoints in cervical carcinomas. DNA helix flexibility clusters were also found near known MYC translocation breakpoints in Burkitt lymphomas (BL), but most BL breakpoints mapped clearly outside FRA8C. Our data revealed that FRA8C is involved in HPV integration and chromosomal translocations in cervical carcinoma; however, this fragile site is not involved in classical MYC translocations in most BLs. In the context of the familial nature of cervical cancer, FRA8C may be considered a candidate susceptibility region for cervical carcinoma.     

Somatic von hippel-lindau mutation in clear cell papillary cystadenoma of the epididymis

Papillary cystadenoma of the epididymis is an uncommon benign lesion that may occur sporadically or as a manifestation of von Hippel—Lindau (VHL) disease. Neither immunohistochemical studies nor molecular genetic analyses of the VHL gene have been reported previously for this lesion. The authors describe two cases of clear cell papillary cystadenoma of the epididymis, both of which were initially confused with metastatic renal cell carcinoma. Both lesions showed positive immunohistochemical staining for low and intermediate molecular weight keratins (Cam 5.2 and AE1/AE3), EMA, vimentin, α₁-antitrypsin, and α₁-antichymotrypsin. Each was negative for CEA. Because clear cell papillary cystadenoma is similar to renal cell carcinoma histologically, and because both occur as components of the von Hippel—Lindau disease complex, the authors analyzed both cases for the presence of mutations in the VHL gene. A somatic VHL gene mutation was detected in one of the two tumors by polymerase chain reaction followed by single-strand conformation polymorphism analysis. Direct sequencing revealed a cytosine to thymine transition at nucleotide 694, resulting in the replacement of an arginine with a stop codon after the sixth amino acid of exon 3. As the VHL gene is believed to function as a tumor suppressor gene, VHL gene mutations may play a role in the initiation of tumorigenesis in sporadic cystadenomas of the epididymis.     

Analysis of susceptibility of mature human T lymphocytes to dexamethasone-induced apoptosis

We present evidence that dexamethasone (Dex), a synthetic glucocorticosteroid, causes apoptosis in mature human T cells, similarly to what has been reported for murine T lymphocytes. Human T cell clones and short-term activated T lymphocytes treated with Dex show the characteristic pattern of apoptotic cells, such as hypodiploid nuclei, chromatin condensation and DNA fragmentation into oligonucleosomal fragments. However, Dex susceptibility of T cells to apoptosis is cell cycle-dependent. The progression in the proliferative cell cycle (G1 versus S) rescues Dex-treated T cells from apoptosis. Moreover, occupancy of the T cell receptor reverses Dex-induced apoptotic phenomena. These observations suggest that glucocorticoids contribute to the regulation of the proliferative or the suicidal response of antigen-activated human T cells.     

Performance of a commercial, type-specific enzyme-linked immunosorbent assay for detection of herpes simplex virus type 2-specific antibodies in Ugandans

Two hundred forty-eight human immunodeficiency virus (HIV)-positive and 496 HIV-negative subjects in Uganda were tested by HerpeSelect herpes simplex virus type 2 enzyme-linked immunosorbent assay (ELISA) and Western blotting to optimize the ELISA for use in this population. A higher index cutoff value was required for optimal sensitivity and specificity, and overall performance of the assay was not affected by HIV status.