Prospective clinical audit of chloral hydrate administration practices in a neonatal unit

Aim: Chloral hydrate is generally considered a safe and effective single dosing procedural sedative for neonates in the clinical setting. However, its safety profile as a repetitive dosing maintenance sedative is largely unknown. This study aimed to document current administration practices of chloral hydrate in the Neonatal Unit, Royal Children's Hospital, Melbourne, Australia, over a 6-month period.

Methods: Patients who had been prescribed chloral hydrate during the specified audit period were recruited into the study and prospectively followed for a period of 28 days, or until they were discharged from the unit. Demographic data were collected on recruitment, and daily documentation of chloral hydrate administration was recorded.

Results: A total of 238 doses of chloral hydrate were administered to a cohort of 32 patients during the study period. The majority of the audited doses (84%) were ordered as repeating doses. Doses were more likely to be given at night than during the day, and the median dosage for repetitive dosing was found to be above the study site's recommended dosing range. Pre-dose and/or post-dose assessment of distress/agitation accompanied dosage approximately half of the time. The audit did not reveal any recognisable pattern of sedation maintenance or weaning process for patients who received multiple doses.

Conclusions: Health-care professionals caring for hospitalised infants should be made aware of the potential risks of chloral hydrate as a repetitive dosing sedative, and of the importance of systematically evaluating the appropriateness and effectiveness of utilising such pharmacological intervention for managing and treating distress.

Utilization of analgesics, sedatives, and pain scores in infants with a prolonged hospitlaization: A prospective descriptive cohort study

Aim
Describe the utilization of analgesic and sedative medications and documentation of pain scores in a cohort of critically ill infants in a neonatal intensive care unit.

Method
A prospective, longitudinal, cohort study of infants with a predicted length of stay =28 days. Dosages and routes of administration of analgesic and sedative medications and documentation of pain scores were collected on a daily basis.

Results
55 infants were enrolled into the study. Oral sucrose was administered to all 55 infants, 51 infants (93%) were administered enteral acetaminophen and 50 (91%) infants were administered morphine during their hospitalization. Sedatives were administered to 42 infants (76%); 36 (65%) were administered chloral hydrate and 32 (58%) were administered intravenous midazolam. With the exception of the first week of admission, when there was highest utilization of opioids and lower use of sucrose, acetaminophen and sedatives, the pattern of administration of analgesic and sedative agents remained relatively constant throughout the hospitalization. Pain scores were documented for 36 (65%) infants during their hospitalisation, however for these 36 infants, pain scores were infrequently recorded.

Conclusion
There was substantial and varied analgesic and sedative use in this cohort of infants, yet infrequent documentation of pain assessment scores. These practices highlight important clinical implications for sick infants requiring careful consideration of pain and distress management.

DESCRIBING SLEEP AND SEDATION PRACTICES IN THE ICU: A MULTINATIONAL SURVEY

Introduction Sleep disturbances are common in critically ill patients treated in the intensive care unit (ICU) with the potential for serious consequences and long-term effects on health outcomes and patient morbidity.
Objectives Our aim was to describe sleep management and sedation practices of adult ICUs in ten countries and to evaluate roles and responsibilities of the ICU staff in relation to key sleep and sedation decisions.
Methods A multicenter, self-administered survey sent to nurse managers of adult ICUs across 10 countries. The questionnaire comprised four domains: sleep characteristics of the critically ill; sleep and sedation practices; non-pharmacological and pharmacological interventions used to improve sleep; and the autonomy and influence of nurses on sleeping practices in the ICU.
Results Overall response rate was 66% (range 32% UK to 100% Cyprus), providing data from 522 ICUs. In all countries, the most frequent patient characteristic perceived to identify sleep was lying quietly with closed eyes (N=409, 78%) (range 92% Denmark to 36% Italy). The most commonly used sedation scale was the Richmond Agitation-Sedation Score (RASS) (N=220, 42%) (range 81% UK to 0% Denmark, Cyprus where most ICUs used the Ramsay score). In most ICUs, selection of sleep medication (N=265, 51%) and assessment of effect (N=309, 59%) was performed by physicians and nurses based on collaborative discussion. In a minority of ICUs (N=161, 31%), decisions and assessments were made by physicians alone. The most commonly used (in all countries) non-pharmacological intervention to promote sleep was reducing ICU staff noise (N=473, 91%) (range 100% Denmark, Norway to 78% Canada). Only 95 ICUs (18%) used earplugs on a frequent basis (range 0% Greece, Cyprus, Denmark to 57% Sweden). Propofol was the drug used most commonly for sedation (N=359, 69%) (range 96% Sweden to 29% Canada). Chloral hydrate was used by only 63 (12%) ICUs (range 0% Greece, Cyprus, Denmark, Italy to 56% Germany). Sedation scales were used on a routine basis by 77% of the 522 ICUs. Participants scored nursing autonomy for sleep and sedation management as moderate; median score of 5 (scale of 0 to 10), range 7 (Canada, Greece, Sweden) to 4 (Norway, Poland). Nursing influence on sleep and sedation decisions was perceived considerable; median score 8, range 9 (Denmark) to 5 (Poland).
Conclusions We found considerable across country variation in sleep promotion and sedation management practices though most have adopted a sedation scale as recommended in professional society guidelines. Most ICUs in all countries used a range of pharmacological and non-pharmacological interventions to promote sleep. Most units reported inter-professional decision-making with nurses perceived to have substantial influence on sleep/sedation decisions.

New families of enantiopure cyclohexenone cis-diol, o-quinol dimer and hydrate metabolites from dioxygenase-catalysed dihydroxylation of phenols

Toluene dioxygenase-catalysed cis-dihydroxylation of phenols has led to the discovery of new enantiopure cyclohexenone cis-diol, o-quinol dimer and phenol hydrate metabolites having synthetic potential.

EFFECT OF ULTRASOUND ON THE KINETICS OF REDUCTION OF HEXACYANOFERRATE(III) BY THIOSULFATE IONS MEDIATED BY RUTHENIUM DIOXIDE HYDRATE

Ultrasound promotes the reduction of hexacyanoferrate(III) by thiosulfate ions mediated by RuO2 . xH(2)O under diffusion-controlled conditions. There is a strong correlation between the measured first-order rate constant and the absorbance of the dispersion, which, in turn, is closely related to the specific surface area of the catalyst. The enhancement in rate with ultrasonic irradiation appears to be largely associated with the dispersive action of the ultrasound on the aggregated particles of RuO2 . xH(2)O. The rate of reaction increases with increasing %duty cycle and ultrasonic intensity. The measured overall activation energies for the reaction with and without ultrasound, i.e. 18 +/- 1 and 20 +/- 1 kJ mol(-1), respectively, are very similar to those expected for a diffusion-controlled reaction. The homogeneous reaction is not promoted by ultrasound.

KINETICS OF REDUCTION OF HEXACYANOFERRATE(III) BY THIOSULFATE IONS MEDIATED BY RUTHENIUM DIOXIDE HYDRATE

The kinetics of reduction of hexacyanoferrate(III) by excess thiosulfate, mediated by RuO2.xH2O, are investigated. At high concentrations of S2O32- (0.1 mol dm-3) the kinetics of Fe(CN)63- reduction are first order with respect to [Fe(CN)63-] and [RuO2.xH2O] and independent of [Fe(CN)64-], [S2O32-] and [S4O62-]. At relatively low concentrations Of S2O32- (0.01 mol dm-3) and in the presence of appreciable concentrations of Fe(CN)64- and S4O62- (0.01 mol dm-3) the kinetics depend directly upon [Fe(CN)63-] and [RuO2.xH2O] and inversely upon [Fe(CN)64-]. Both sets of kinetics can be rationalised using an electrochemical model of redox catalysts in which a reversible reduction reaction [Fe(CN)63- + e- --> Fe(CN)64-] is coupled to an irreversible oxidation reaction (s2O32- - e- --> 1/2S4O62-), by a dispersion of RuO2.xH2O microelectrodes. At high concentrations Of S2O32- this model predicts that the kinetics of Fe(CN)63- reduction are controlled by the rate of diffusion of the Fe(CN)63- ions to the RuO2.xH2O particles. The kinetics observed at low concentrations of S2O32- are predicted by the electrochemical model, assuming that the Tafel slope for the oxidation Of S2O32- to S4O62- on the RuO2.xH2O particles is 56.4 mV decade-1.

OXIDATION OF RUTHENIUM(II) TRIS(2,2'-BIPYRIDINE) IONS BY THALLIC IONS IN NITRIC-ACID, MEDIATED BY RUTHENIUM DIOXIDE HYDRATE - AN EXAMPLE OF REVERSIBLE HETEROGENEOUS REDOX CATALYSIS

The kinetics of the oxidation of Ru(bpy)32+ to Ru(bpy)33+ by T13+ ions, catalyzed by a dispersion of RuO2-xH2O in 3 mol dm-3 HNO3, are reported as a function of [Ru(bpy)32+], [Tl3+], [Tl+], [RuO2.xH2O], and temperature. The kinetics of Ru(bpy)32+ oxidation fit an electrochemical model of redox catalysis involving electron transfer between the two electrochemically reversible redox couples, i.e. Ru(bpy)33+/Ru(bpy)32+ and Tl3+/Tl+, mediated by the dispersion of microelectrode particles of RuO2.xH2O. In this model, the rate of reaction is assumed to be controlled by the diffusion of Ru(bpy)32+ toward, and Ru(bpy)33+ away from, the catalyst particles. The Arrhenius activation energy for the catalyzed reaction is 25.9 +/- 0.7 kJ mol-1, and the changes in enthalpy and entropy for the reaction are 36 +/- 2 kJ mol-1 and 127 +/- 6 J mol-1 K-1, respectively. This work describes a rare example of reversible heterogeneous redox catalysis.

OXIDATIVE DISSOLUTION OF RUTHENIUM DIOXIDE HYDRATE BY PERIODATE IONS

The results of a kinetic study of the oxidative dissolution of ruthenium dioxide hydrate to ruthenium tetroxide by periodate ions, IO4-, in acidic solution are described. The kinetics of dissolution give a good fit to a 'soft-centre' model in which the particles of RuO2.xH2O are assumed to be monodispersed, spherical but inhomogeneous in composition, comprising a difficult-to-corrode outer shell and a more easy-to-corrode inner core. In this work metaperiodate appears to act as a two-electron oxidant. The observed kinetics fit a reaction scheme in which the rate-determining step is the reaction between a surface site and an adsorbed IO4 ion and there is competitive adsorption by any IO3- present. In the absence and presence of an excess of IO3- ions, the overall activation energy for the corrosion reaction was determined to be 38 +/- 2 and 54 +/- 4 kJ mol-1, respectively.

OXIDATION OF WATER BY MNO4- MEDIATED BY THERMALLY ACTIVATED RUTHENIUM DIOXIDE HYDRATE

The kinetics of oxidation of water to oxygen by MnO4-, mediated by thermally activated ruthenium dioxide hydrate, has been studied. The rate of catalysis is 0.8 order with respect to the surface concentration of MnO4- (which in turn appears to fit a Langmuir adsorption isotherm) and proportional to the catalyst concentration, but is independent of the concentration of manganese(II) ions. The catalysed reaction appears to have an activation energy of 50 +/- 1 kJ mol-1. These observed kinetics are readily rationalised using an electrochemical model in which the catalyst particles act as microelectrodes providing a medium for electron transfer between the highly irreversible oxidation of water to O2 and the highly irreversible reduction of MnO4- to Mn2+.

KINETICS OF CORROSION OF RUTHENIUM DIOXIDE HYDRATE BY CEIV IONS

The kinetics of oxidative dissolution of RuO2 .xH2O to RuO4 by Ce(iv) ions are studied. Under conditions of a low [Ce(iv)] : [RuO2 .xH2O] ratio (e.g. 0.35 : 1) and a high background concentration of Ce(III) ions (which impede dissolution) the initial reduction of Ce(iv) ions is due to charging of the RuO2 .xH2O microelectrode particles. The initial rate of charging depends directly upon [RuO2 .xH2O] and has an activation energy of 25 +/- 5 kJ mol-1 Under conditions of a high [Ce(iv] : [RuO2 .xH2O] (e.g. 9 : 1) and a low background [Ce(III] the reduction of Ce(iv) ions is almost totally associated with the dissolution of RuO2 .xH2O to RuO4, i.e. not charging. The kinetics of dissolution obey an electrochemical model in which the reduction of Ce(iv) ions and the oxidation of RuO2 .xH2O to RuO4 are assumed to be highly reversible and irreversible processes, respectively, mediated by dissolving the microelectrode particles of RuO2 .xH2O. Assuming this electrochemical model, from an analysis of the kinetics of dissolution the activation energy for this process was estimated to be 39 +/- 5 kJ mol-1 and the Tafel slope for RuO2 .xH2O corrosion was calculated to be 15 mV per decade. The mechanistic implications of these results are discussed.