Effectiveness and harms of pharmacological interventions for the treatment of delirium in adults in intensive care units after cardiac surgery: a systematic review.

OBJECTIVE: The objective of this review was to synthesize the best available evidence on the effectiveness and harms of pharmacological interventions for the treatment of delirium in adult patients in the intensive care unit (ICU) after cardiac surgery. INTRODUCTION: Patients who undergo cardiac surgery are at high risk of delirium (incidence: 50-90%). Delirium has deleterious effects, increasing the risk of death and adversely affecting recovery. Clinical interventional trials have been conducted to prevent and treat postoperative delirium pharmacologically including antipsychotics and sedatives. These trials have provided some evidence about efficacy and influenced clinical decision making. However, much reporting is incomplete and provides biased assessments of efficacy; benefits are emphasized while harms are inadequately reported. INCLUSION CRITERIA: Participants were ≥ 16 years, any sex or ethnicity, who were treated postoperatively in a cardiothoracic ICU following cardiac surgery and were identified as having delirium. Any pharmacological intervention for the treatment of delirium was included, regardless of drug classification, dosage, intensity or frequency of administration. Outcomes of interest of this review were: mortality, duration and severity of delirium, use of physical restraints, quality of life, family members' satisfaction with delirium management, duration/severity of the aggressive episode, associated falls, severity of accidental self-harm, pharmacological harms, harms related to over-sedation, ICU length of stay, hospital length of stay (post ICU), total hospital length of stay, need for additional intervention medication and need for rescue medication. Randomized controlled trials were considered first and in their absence, non-randomized controlled trials and quasi-experimental would have been considered, followed by analytical observational studies. METHODS: A search was conducted in PubMed, Embase, CINAHL, Web of Science, Cochrane Central Register of Controlled Trials, Scopus, Epistemonikos, Australian New Zealand Clinical Trials Registry, ClinicalTrials.gov, Clinical Trials in New Zealand, and ProQuest Dissertations and Theses to locate both published and unpublished studies. There was no date limit for the search. A hand search for primary studies published between January 1, 2012 and November 17, 2018 in relevant journals was also conducted. Only studies published in English were considered for inclusion. Two reviewers independently assessed the methodological quality using standardized critical appraisal instruments from JBI and McMaster University. Quantitative data were extracted using the standardized JBI data extraction tool. A meta-analysis was not performed, as there was too much clinical and methodological heterogeneity in the included studies. Results have been presented in a narrative form. Standard GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) evidence assessment of outcomes has been reported. RESULTS: Three RCTs investigating morphine versus haloperidol (n = 53), ondansetron versus haloperidol (n = 72), and dexmedetomidine versus midazolam (n = 80) were included. Due to heterogeneity and incomplete reporting, a meta-analysis was not feasible. Overall, the methodological quality of these studies was found to be low. Additionally, this review found reporting of harms to be inadequate and superficial for all three studies and did not meet the required standards for harms reporting, as defined by the CONSORT statement extension for harms. CONCLUSIONS: It was not possible to draw any valid conclusions regarding the effectiveness of morphine vs haloperidol, ondansetron vs haloperidol or dexmedetomidine vs midazolam in treating delirium after cardiac surgery. This is due to the low number of studies, the poor methodological quality in conducting and reporting and the heterogeneity between the studies.

Effectiveness and harms of pharmacological interventions in the treatment of delirium in adults in intensive care units post cardiac surgery: a systematic review protocol.

REVIEW QUESTION/OBJECTIVE: The review objective is to synthesize the best available evidence on the effectiveness and harms of pharmacological interventions in the treatment of delirium in adults in intensive care units (ICU) after cardiac surgery.The specific review question is: What is the effectiveness and what are the harms of pharmacological interventions in relation to the duration and severity of delirium episodes, length of stay in ICU, length of stay in hospital, functional capacity and quality of life and mortality for critically ill adult patients treated in intensive care after cardiac surgery?

Solvent-dependent switch of ligand donor ability and catalytic activity of ruthenium(II) complexes containing pyridinylidene amide (PYA) N-heterocyclic carbene hybrid ligands.

Chelating ligands incorporating both N-[1-alkylpyridin-4(1H)-ylidene]amide (PYA) and N-heterocyclic carbene (NHC) donor sites were prepared and used for the synthesis of ruthenium(II) complexes. Cyclic voltammetry, NMR, and UV-vis spectroscopy of the complexes indicate a solvent-dependent contribution of the limiting resonance structures associated with the ligand in solution. The neutral pyridylidene imine structure is more pronounced in apolar solvents (CH2Cl2), while the mesoionic pyridinium amide form is predominant in polar solvents (MeOH, DMSO). The distinct electronic properties of these hybrid PYA-NHC ligands in different solvents have a direct influence on the catalytic activity of the ruthenium center, e.g., in the dehydrogenation of benzyl alcohol to benzaldehyde. The activity in different solvents qualitatively correlates with the solvent permittivity.

Synthesis, structural, photophysical and electrochemical studies of various d-metal complexes of btp [2,6-bis(1,2,3-triazol-4-yl)pyridine] ligands that give rise to the formation of metallo-supramolecular gels.

2,6-Bis(1,2,3-triazol-4-yl)pyridine (btp) is a terdentate binding motif that is synthesised modularly via the CuAAC reaction. Herein, we present the synthesis of ligands 1 and 2 and the investigation of the coordination chemistry, photophysical behaviour and electrochemistry of complexes of these with a number of d-metal ions (e.g. Ru(II), Ir(III), Ni(II) and Pt(II)). The X-ray crystal structures of ligand 1 and the complexes [Ru·2(2)](PF6)Cl, [Ni·1(2)](PF6)Cl and [Ir·1Cl3] are also presented. All of the complexes displayed non-classical triazolyl C-H···Cl(-) hydrogen bonding. All but one complex showed no metal-based luminescence at room temperature, while all of the Pt(ii) complexes displayed luminescence at 77 K. The electrochemistry of the Ru(II) complexes was also studied and these complexes were found to have higher oxidation potentials than analogous compounds. The redox behaviour of [RuL2](2+) complexes with both 1 and 2 was nearly identical, while [Ru·1Cl2(DMSO)] was oxidised at significantly lower potential. We also show that the Ru(II) complex of 2, [Ru·2(2)](PF6)Cl, gave rise to the formation of a metallo-supramolecular gel, the morphology of which was studied using scanning electron and helium ion microscopy.

Synthesis, photo-, and electrochemistry of ruthenium bis(bipyridine) complexes comprising a N-heterocyclic carbene ligand.

Analogues of [Ru(bpy)3](2+) were prepared in which one pyridine ligand site is substituted by a N-heterocyclic carbene (NHC) ligand, that is, either by an imidazolylidene with a variable wingtip group R (R = Me, 3a; R = Et, 3b; R = iPr, 3c), or by a benzimidazolylidene (Me wingtip group, 3d), or by a 1,2,3-triazolylidene (Me wingtip group, 3e). All complexes were characterized spectroscopically, photophysically, and electrochemically. An increase of the size of the wingtip groups from Me to Et or iPr groups distorts the octahedral geometry (NMR spectroscopy) and curtails the reversibility of the ruthenium oxidation. NHC ligands with methyl wingtip groups display reversible ruthenium oxidation at a potential that reflects the donor properties of the NHC ligand (triazolylidene > imidazolylidene > benzimidazolylidene). The most attractive properties were measured for the triazolylidene ruthenium complex 3e, featuring the smallest gap between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) in the series (2.41 eV), a slightly red-shifted absorption profile, and reasonable excited-state lifetime (188 ns) when compared to [Ru(bpy)3](2+). These features demonstrate the potential utility of triazolylidene ruthenium complexes as photosensitizers for solar energy conversion.