Effect of local infiltration analgesia, peripheral nerve blocks, general and spinal anesthesia on early functional recovery and pain control in total knee arthroplasty.

BACKGROUND: Postoperative pain control and enhanced mobilization, muscle strength and range of motion following total knee arthroplasty (TKA) are pivotal requisites to optimize rehabilitation and early recovery. The aim of the study was to analyze the effect of local infiltration analgesia (LIA), peripheral nerve blocks, general and spinal anesthesia on early functional recovery and pain control in primary total knee arthroplasty. METHODS: Between January 2016 until August 2016, 280 patients underwent primary TKA and were subdivided into four groups according to their concomitant pain and anesthetic procedure with catheter-based techniques of femoral and sciatic nerve block (group GA&FNB, n = 81) or epidural catheter (group SP&EPI, n = 51) in combination with general anesthesia or spinal anesthesia, respectively, and LIA combined with general anesthesia (group GA&LIA, n = 86) or spinal anesthesia (group SP&LIA, n = 61). Outcome parameters focused on the evaluation of pain (NRS scores), mobilization, muscle strength and range of motion up to 7 days postoperatively. The cumulative consumption of (rescue) pain medication was analyzed. RESULTS: Pain relief was similar in all groups, while the use of opioid medication was significantly lower (up to 58%) in combination with spinal anesthesia, especially in SP&EPI. The LIA groups, in contrast, revealed significant higher mobilization (up to 26%) and muscle strength (up to 20%) in the early postoperative period. No analgesic technique-related or surgery-related complications occurred within the first 7 days. Due to insufficient pain relief, 8.4% of the patients in the catheter-based groups and 12.2% in the LIA groups resulted in a change of the anesthetics pain management. CONCLUSIONS: The LIA technique offers a safe and effective treatment option concerning early functional recovery and pain control in TKA. Significant advantages were shown for mobilization and muscle strength in the early postoperative period while pain relief was comparable within the groups.

Effect of local infiltration analgesia, peripheral nerve blocks, general and spinal anesthesia on early functional recovery and pain control in unicompartmental knee arthroplasty.

BACKGROUND: The aim of the study was to analyze the effect of local infiltration analgesia (LIA), peripheral nerve blocks, general and spinal anesthesia on early functional recovery and pain control in primary unicompartmental knee arthroplasty (UKA). METHODS: Between January 2016 until August 2016, 134 patients underwent primary UKA and were subdivided into four groups according to their concomitant pain and anesthetic procedure with catheter-based techniques of femoral and sciatic nerve block (group GA&FNB, n = 38) or epidural catheter (group SP&EPI, n = 20) in combination with general anesthesia or spinal anesthesia, respectively, and LIA combined with general anesthesia (group GA&LIA, n = 46) or spinal anesthesia (group SP&LIA, n = 30). Outcome parameters focused on the evaluation of pain (NRS scores), mobilization, muscle strength and range of motion up to 7 days postoperatively. The cumulative consumption of (rescue) pain medication was analyzed. RESULTS: The LIA groups revealed significantly lower (about 50%) mean NRS scores (at rest) compared to the catheter-based groups at the day of surgery. In the early postoperative period, the dose of hydromorphone as rescue pain medication was significantly lower (up to 68%) in patients with SP&EPI compared to all other groups. No significant differences could be detected with regard to grade of mobilization, muscle strength and range of motion. However, there seemed to be a trend towards improved mobilization and muscle strength with general anesthesia and LIA, whereof general anesthesia generally tended to ameliorate mobilization. CONCLUSIONS: Except for a significant lower NRS score at rest in the LIA groups at day of surgery, pain relief was comparable in all groups without clinically relevant differences, while the use of opioids was significantly lower in patients with SP&EPI. A clear clinically relevant benefit for LIA in UKA cannot be stated. However, LIA offers a safe and effective treatment option comparable to the well-established conventional procedures.

Cloning, site-specific mutagenesis, expression and characterization of full-length chloroplast NADP-malate dehydrogenase from Pisum sativum.

Chloroplast NADP-dependent malate dehydrogenase is regulated by a dithiol redox reaction. The assignment of the groups involved, requires the primary structure of the enzyme to be known. Using the polymerase chain reaction and the cDNA library of Pisum sativum, the sequence of the enzyme and its targeting signal was determined. The gene was cloned in Escherichia coli JM83 and expressed in E. coli JM83 and E. coli B at high yield. The determination of the physical properties of the gene product proves the recombinant protein to be indistinguishable from the enzyme purified from the plant. This holds true, in spite of the fact that the plant enzyme lacks 11 N-terminal residues. The lengths of the complete polypeptide chain of the recombinant enzyme and its transit peptide are 388 and 53 residues, respectively. The comparison of the sequences of the mature enzyme with those of known chloroplast NADP-MDH shows 83-95% identity, but with mitochondrial or bacterial MDH only approximately 20%. Reduction of the (inactive) oxidized enzyme with dithiothreitol allows mimicking of the in vivo activation. The reaction follows a consecutive second-order-kinetics mechanism. Guanidinium chloride (GdmCl) at concentrations below 0.4 M leads to a significant activation of the oxidized form of the enzyme. At [GdmCl] = 0.4-0.46 M, both oxidized and reduced NADP-MDH show highly cooperative changes in the hydrodynamic and spectral properties, indicating the synchronous breakdown of the quaternary, tertiary and secondary structures. Site-directed mutations C23A and C28A do not quench the regulatory properties of the enzyme; additional substitution of alanine for Cys206 and Cys376 renders the enzyme equally active in both the reduced and the oxidized state. Therefore, one can consider these residues, either alone or in combination with Cys23 and Cys28, as responsible for enzyme activation.

Structural and catalytic properties of oxidized and reduced chloroplast NADP-malate dehydrogenase upon denaturation and renaturation.

Chloroplast NADP-dependent malate dehydrogenase exists in two interconvertible forms: the inactive disulfide-containing form and the active dithiol form. No major difference in secondary structure or conformation was found between the oxidized and the reduced enzyme as determined by circular dichroism and intrinsic protein fluorescence. The guanidine/HCl-dependent unfolding of the enzyme is characterized by two transition midpoints: those of the reduced enzyme are lower by about 0.2 M guanidine/HCl compared to the oxidized enzyme. As shown by analytical ultracentrifugation, there was no effect of guanidine/HCl concentrations up to 0.25 M on the quaternary structure of the enzyme in its oxidized and reduced forms: both sedimentation coefficient (S20,w = 4.9 +/- 0.1 S) and sedimentation equilibrium (75 +/- 3 kDa) yield the dimer. In the oxidized state the enzyme undergoes guanidine-dependent dissociation to the monomer with a midpoint of transition at 0.5 M. The kinetics of unfolding were found to be significantly faster for the reduced than for the oxidized enzyme. Renaturation and reactivation of reduced enzyme was more rapid and occurred with higher yields (100%) than for the oxidized enzyme (60-80% yield). Furthermore, the effect of denaturants on catalytic activity, and reductive activation of the oxidized form, were studied. Both increase in protein fluorescence and a stimulatory effect on the activities at low guanidine/HCl concentrations were observed for the oxidized and the reduced form of the enzyme. Denaturants increase the rate of reductive activation of NADP-malate dehydrogenase.