Effect of volatile versus propofol anaesthesia on major complications and mortality after cardiac surgery: a multicentre randomised trial.

BACKGROUND: The comparative effectiveness of volatile anaesthesia and total intravenous anaesthesia (TIVA) in terms of patient outcomes after cardiac surgery remains a topic of debate. METHODS: Multicentre randomised trial in 16 tertiary hospitals in China. Adult patients undergoing elective cardiac surgery were randomised in a 1:1 ratio to receive volatile anaesthesia (sevoflurane or desflurane) or propofol-based TIVA. The primary outcome was a composite of predefined major complications during hospitalisation and mortality 30 days after surgery. RESULTS: Of the 3123 randomised patients, 3083 (98.7%; mean age 55 yr; 1419 [46.0%] women) were included in the modified intention-to-treat analysis. The composite primary outcome was met by a similar number of patients in both groups (volatile group: 517 of 1531 (33.8%) patients vs TIVA group: 515 of 1552 (33.2%) patients; relative risk 1.02 [0.92-1.12]; P=0.76; adjusted odds ratio 1.05 [0.90-1.22]; P=0.57). Secondary outcomes including 6-month and 1-yr mortality, duration of mechanical ventilation, length of ICU and hospital stay, and healthcare costs, were also similar for the two groups. CONCLUSIONS: Among adults undergoing cardiac surgery, we found no difference in the clinical effectiveness of volatile anaesthesia and propofol-based TIVA. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR-IOR-17013578).

Cationic poly(VCL-AETA) hydrogels and ovalbumin (OVA) release in vitro.

The objective of this research is to explore the synthesis of a new family of water soluble polycationic copolymeric precursors that could be photo-crosslinked into hydrogels. The in vitro control release of ovalbumin protein (OVA) from this family of hydrogels was also studied to assess the biomedical potential of this new family polycationic hydrogels. A series of novel poly(VCL-AETA) copolymer hydrogels was fabricated in an aqueous medium via photo-induced polymerization and crosslinking of hydrophobic N-vinylcaprolactam (VCL) and hydrophilic [2-(acryloxy)ethyl]trimethylammonium chloride (AETA) monomers over a wide range of VCL to AETA feed molar ratios of 2:1, 1:1, 1:2, 1:5. N,N'-methylene bisacrylamide (MBA) was used as a crosslinker. Ovalbumin (OVA), a model antigen, was preloaded into poly(VCL-AETA) hydrogel precursors and its release profiles in pH 7.4 PBS at 37 degrees C were investigated as a function of VCL to AETA monomer feed ratios over a period of 4 weeks. The in vitro results showed that OVA initial burst and subsequent sustained releases could be controlled by 3 material parameters: the hydrophobic VCL to hydrophilic AETA monomer feed ratios, crosslinking density and hydrogel degradation rate. Thus, the hydrophobic-hydrophilic VCL-AETA hydrogel network for controlled OVA release could offer advantages over organic solvent-based single component polymer system. However, these in vitro OVA release profiles may change in an in vivo environment.

Biodegradable hydrophobic-hydrophilic hybrid hydrogels: swelling behavior and controlled drug release.

The objective of this work was to investigate a new family of hydrophobic-hydrophilic biodegradable hybrid hydrogels as drug carriers. A series of hydrophobic-hydrophilic biodegradable hybrid hydrogels was formulated via photo means from hydrophobic three-arm poly (epsilon-caprolactone) maleic acid (PGCL-Ma) and hydrophilic dextran maleic acid (Dex-Ma) precursors over a wide range of the two precursors' feed ratio (PGCL-Ma/Dex-Ma at 100:0, 70:30, 50:50, 30:70 and 0:100). A low-molecular-weight and hydrophilic drug, the alpha-7 agonist cocaine methiodide, was used as the model drug for the release study from the hybrid hydrogels in pH 7.4 phosphate buffer solution at 37 degrees C. The swelling data of these hybrid hydrogels depended on the hydrophobic to hydrophilic precursors' feed ratio, and there were several-fold differences in swelling ratios between a pure hydrophilic Dex-Ma and a pure hydrophobic PGCL-Ma hydrogels. The presence of the hydrophobic PGCL-Ma component significantly reduced the initial burst swelling of the hybrid hydrogels. Depending on the two precursors' feed ratios, the swelling data during the early period obeyed either Fickian diffusion (for 50:50 PGCL-Ma/Dex-Ma hydrogel), non-Fickian or anomalous transport (for 70:30 and 100:0 PGCL-Ma/Dex-Ma), or relaxation-controlled (for 30:70 and 0:100 PGCL-Ma/Dex-Ma). A wide range of cocaine methiodide release profiles was achieved by controlling hydrophobic to hydrophilic precursors' feed ratios. Initial drug burst release was significantly reduced as the concentration of the hydrophobic PGCL-Ma component increased in the hybrid hydrogels. The bulk of cocaine methiodide released during the 160-h period was via diffusion-controlled mechanism, while degradation-controlled mechanism dominated thereafter.

Synthesis and characterization of partially biodegradable and thermosensitive hydrogel.

A partially biodegradable and thermosensitive hybrid hydrogel network (DAN series) based on dextran-allylisocyanate (Dex-AI) and poly(N-isopropylacrylamide) (PNIPAAm) was synthesized via UV photocrosslinking. These hybrid hydrogels were characterized in terms of their chemical structure, thermal, mechanical, morphological and temperature-induced swelling properties. The effect of the composition ratio of Dex-AI to PNIPAAm on such properties were examined. The differential scanning calorimetry data show that this Dex-AI/PNIPAAm hybrid network has an increased lower critical solution temperature (LCST) and glass transition temperature (Tg) with an increase in the Dex-AI content. The interior morphology of these hybrid hydrogels revealed a decreased porous microstructure with an increase in the Dex-AI content in the hybrid network. Furthermore, if the Dex-AI composition became too high, a distinctive network structure with two different microporous structures appeared. The mechanical properties of these hybrid hydrogels also increased with an increase in the Dex-AI content. The temperature dependence of the swelling ratio, the deswelling kinetics as well as the reswelling kinetics was also characterized by gravimetric method. When comparing with a normal PNIPAAm hydrogel, these Dex-AI/PNIPAAm hybrid networks, due to the presence of Dex-AI moiety, also show improved temperature-induced intelligent properties, such as the faster and controllable response dynamics, which may find promising applications in a wide variety of fields, such as biomedical and bioengineering fields.

Synthesis, characterization and controlled drug release of thermosensitive IPN-PNIPAAm hydrogels.

A method was developed to prepare thermosensitive poly(N-isopropylacrylamide) (PNIPAAm) hydrogels with an interpenetrating polymer network (IPN) structure for the purpose of improving its mechanical properties, response rate to temperature and sustained release of drugs. Although the differential scanning calorimetry data exhibited similarly lower critical solution temperature (LCST) between IPN- and non-IPN-PNIPAAm hydrogels, an increase in the glass transition temperature (Tg) of the IPNs relative to the normal PNIPAAm hydrogel was observed. In addition, the mechanical properties of the IPNs were greatly improved when compared with the normal PNIPAAm hydrogel. The interior morphology of the IPN-PNIPAAm hydrogels was revealed by scanning electron microscopy (SEM); the IPN hydrogels showed a fibrillar-like porous network structure that normal PNIPAAm did not have. Furthermore, by measuring the temperature dependence of the swelling ratio and deswelling kinetics, these IPN hydrogels also exhibited improved intelligent characteristics (e.g., controllable faster response rate) that depended on the composition ratio of the two network components. From the applications viewpoint, the effects of a shrinking-reswelling cycle around the LCST on the properties of the IPN hydrogels were examined to determine if these properties would be stable for potential applications. Bovine serum albumin was chosen as the model protein for examining its release from the IPNs at different temperatures. The release data suggested that an improved controlled release could be achieved by the IPN-PNIPAAm hydrogels without losing their intelligent properties.