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.     

Comparison of the structure of human intervertebral discs in the cervical,thoracic and lumbar regions of the spine

Posterior and anterior heights, cross-sectional area and shape were measured for all the intervertebral discs in four spines from elderly human cadavers. Disc height was a minimum at the T4-5 level; thoracic discs were less wedge-shaped than those in the cervical and lumbar regions. Cross-sectional area increased from the cranial to caudal extremity; at the L5-S1 level the nucleus pulposus occupied a high proportion of this area. Cervical discs tended to have an elliptical cross-sectional shape, thoracic discs were more circular and lumbar discs tended to have an elliptical cross-section which was flattened or re-entrant posteriorly. This shape distribution was quantified by defining a shape index which had a maximum value of 1 for a circular cross-section. Orientations of the reinforcing fibres in the outer lamellae of the anterior annulus fibrosus were measured from 27 discs by X-ray diffraction. For these measurements, C3-4, T7-8 and L2-3 were chosen as representative of cervical, thoracic and lumbar discs. The fibre tilt, with respect to the axis of the spine, was significantly less in the cervical discs (at 65 degrees) than in the thoracic and lumbar discs (about 70 degrees). These findings are interpreted in relation to differing functional requirements and possible mechanisms of failure in the cervical, thoracic and lumbar regions of the spine in the light of current knowledge on the biomechanics of the intervertebral disc.     

Study of nuclear diameters in non-Hodgkin's lymphomas

The mean maximum nuclear diameter (D_max) in 21 cases of non-Hodgkin's lymphoma (NHL) has been determined, using the Reichert-Jung (Kontron) MOP-AMO₃ user-controlled image analyser. Nuclear diameters of high-grade malignancy NHL were found to be considerably greater than those of low-grade malignancy lymphomas, although there was some overlap of their ranges. These findings confirm objectively subjective estimates of nuclear size in NHL. The relative usefulness of the user-controlled (interactive) image analyser for the measurement of nuclei in tissue sections is compared with that of a fully automatic machine.     

Preliminary report of an ultrasonography and colour Doppler uterine score to predict uterine receptivity in an in-vitro fertilization programme

A total of 96 women undergoing in-vitro fertilization (IVF) treatment were examined by transvaginal ultrasonography with colour and pulsed Doppler ultrasound on the 22nd day of the menstrual cycle preceding IVF. We assessed endometrial thickness, endometrial morphology, myometrial echogenicity, subendometrial vascularization, the uterine artery pulsatility index, protodiastolic notch and end diastolic blood flow in order to define a uterine score which could be correlated with the pregnancy rate. The overall pregnancy rate was 30.2%, and there was no difference between the pregnant and non-pregnant groups with regard to any of the ultrasonographic and Doppler parameters when examined separately. However, the uterine score was significantly higher in the pregnant group (15.9 +/- 2.81 versus 12.7 +/- 5.3, P = 0.002; t-test). No pregnancy occurred if the score was between 0 and 10. With a score of 11-15 there was a 34.7% chance of pregnancy, and scores >16 had a 42% chance of pregnancy. In conclusion, individual ultrasonographic and Doppler parameters are not of sufficient accuracy to predict uterine receptivity. The uterine score calculated prior to IVF cycles appears to be a useful predictor of implantation.      

Molecular basis of phenylketonuria and related hyperphenylalaninemias: mutations and polymorphisms in the human phenylalanine hydroxylase gene.

Mutations in the human phenylalanine hydroxylase gene producing phenylketonuria or hyperphenylalaninemia have now been identified in many patients from various ethnic groups. These mutations all exhibit a high degree of association with specific restriction fragment-length polymorphism haplotypes at the PAH locus. About 50 of these mutations are single-base substitutions, including six nonsense mutations and eight splicing mutations, with the remainder being missense mutations. One splicing mutation results in a 3 amino acid in-frame insertion. Two or 3 large deletions, 2 single codon deletions, and 2 single base deletions have been found. Twelve of the missense mutations apparently result from the methylation and subsequent deamination of highly mutagenic CpG dinucleotides. Recurrent mutation has been observed at several of these sites, producing associations with different haplotypes in different populations. About half of all missense mutations have been examined by in vitro expression analysis, and a significant correlation has been observed between residual PAH activity and disease phenotype. Since continuing advances in molecular methodologies have dramatically accelerated the rate in which new mutations are being identified and characterized, this register of mutations will be updated periodically.     

Molecular genetics of PKU in Eastern Europe: A nonsense mutation associated with haplotype 4 of the phenylalanine hydroxylase gene

Phenylketonuria (PKU) is a genetic disorder secondary to a deficiency of hepatic phenyalanine hydroxylase (PAH). Several mutations in thePAH gene have recently been reported, and linkage disequilibrium was observed between RFLP haplotypes and specific mutations. A new molecular lesion has been identified in exon 7 of thePAH gene in a Hungarian PKU patient by direct sequencing of PCR-amplified DNA. The C-to-T transition causes the substitution of Arg²⁴³ to a termination codon, and the mutant allele is associated with haplotype 4 of thePAH gene. The mutation is present in two of nine mutant haplotype 4 alleles among Eastern Europeans and is not present among Western Europeans and Asians. The rarity of this mutant allele and its restricted geographic distribution suggest that the mutational event occurred recently on a normal haplotype 4 background in Eastern Europe.