Rotational thromboelastometry during Cesarean section as a predictive evaluation for the progression of persistent postpartum hemorrhage in parturients with placenta previa: A prospective observational study.

Background: The rotational thromboelastogram (ROTEM) has been used in the management of massive bleeding and transfusion strategy. This study investigated ROTEM parameters measured during Cesarean section as predictors for the progression of persistent postpartum hemorrhage (PPH) in parturients with placenta previa. Methods: This prospective observational study recruited 100 women scheduled for elective Cesarean section after being diagnosed with placenta previa. Recruited women were divided into two groups according to the amount of estimated blood loss: the PPH group (PPH > 1500 ml) vs. the non-PPH group. ROTEM with laboratory tests was performed three times, preoperative, intraoperative, and postoperative time, which were compared between the two groups. Results: The PPH and non-PPH groups included 57 and 41 women, respectively. The area under the receiver-operating characteristic curve of postoperative FIBTEM A5 to detect PPH was 0.76 (95% CI = 0.64 to 0.87; P < 0.001). When postoperative FIBTEM A5 was 9.5, the sensitivity and specificity were 0.74 (95% CI = 0.55 to 0.88) and 0.73 (95% CI = 0.57 to 0.86), respectively. When subgrouping the PPH group based on the postoperative FIBTEM A5 value of 9.5, intraoperative cEBL was similar between the two subgroups; however, postoperative RBC was transfused more in the subgroup with FIBTEM A5 < 9.5 than the subgroup with FIBTEM A5 ≥ 9.5 (7.4 ± 3.0 vs 5.1 ± 2.3 units, respectively; P = 0.003). Conclusion: Postoperative FIBTEM A5, with appropriate selection of the cut-off value, can be a biomarker for more prolonged PPH and massive transfusion following Cesarean section by placenta previa.

Effects of depth of neuromuscular block on surgical conditions during laparoscopic colorectal surgery: a randomised controlled trial.

There have been few objective evaluations of the effects of deep neuromuscular blockade on intra-operative conditions. In this prospective randomised controlled study, we evaluated the effects of deep neuromuscular block on surgical conditions during laparoscopic colorectal surgery. Patients were randomly allocated using a computer-generated randomisation code to either moderate (train-of-four count 1-2 maintained and antagonised with neostigmine) or deep (post-tetanic count 1-2 maintained and reversed with sugammadex) levels of neuromuscular blockade. The primary outcome measure was the number of abrupt increases in intra-abdominal pressure intra-operatively. Secondary outcome variables were intra-operative restoration of spontaneous breathing, number of surgical requests for additional neuromuscular blockade, surgical rating of operating conditions and patient satisfaction. The surgeon who rated the surgical conditions score and investigator who checked the postoperative variables were blinded to patient allocation. In total, we recruited 70 patients of whom 64 (32 in each group) were analysed. Increases in intra-abdominal pressure (14/32 vs. 6/32; p = 0.031), intra-operative restoration of spontaneous breathing (16/32 vs. 2/32; p < 0.001) and request for additional neuromuscular blockade (21/32 vs. 8/32; p = 0.001) were more frequent in the moderate compared with the deep group. In patients undergoing elective laparoscopic colorectal surgery, deep neuromuscular blockade provided better surgical conditions than moderate neuromuscular blockade, as measured by a reduction in the incidence of intra-abdominal pressure alarms.

Porphyromonas gingivalis induces autophagy in THP-1-derived macrophages.

Autophagy provides a mechanism for the turnover of cellular organelles and proteins through a lysosome-dependent degradation pathway and is a possible mechanism in inflammatory disease. Periodontitis is an inflammatory disease caused by periodontal pathogens. Porphyromonas gingivalis, an important periodontal pathogen, activates cellular autophagy to provide a replicative niche while suppressing apoptosis in endothelial cells. However, the molecular basis for a causal relationship between P. gingivalis and autophagy is unclear. This research examines the involvement of P. gingivalis in autophagy through light chain 3 (LC3) and autophagic proteins, and the role of P. gingivalis-induced autophagy in the clearance of P. gingivalis and inflammation. To investigate the molecular mechanism of autophagy induced by P. gingivalis, PMA-differentiated THP-1-derived macrophages were infected with live P. gingivalis. The P. gingivalis increased the formation of autophagosomes in a multiplicity of infection-dependent manner, as well as autophagolysosomes. Porphyromonas gingivalis activated LC3-I/LC3-II conversion and increased the conjugation of autophagy-related 5 (ATG5) -ATG12 and the expression of Beclin1. The expressions of Beclin1, ATG5-ATG12 conjugate, and LC3-II were significantly inhibited by the presence of 3-methyladenine, an autophagy inhibitor. Interestingly, 3-methyladenine increased the survival of P. gingivalis and proinflammatory cytokine interleukin-1ß production. The data indicate that P. gingivalis induces autophagy in PMA-differentiated THP-1-derived macrophages and in turn, macrophages eliminate P. gingivalis through an autophagic response, which can lead to the restriction of an excessive inflammatory response by downregulating interleukin-1ß production. The induction of autophagy by P. gingivalis may play an important role in the periodontal inflammatory process and serve as a target for the development of new therapies.

Magnesium sulphate attenuates acute postoperative pain and increased pain intensity after surgical injury in staged bilateral total knee arthroplasty: a randomized, double-blinded, placebo-controlled trial.

BACKGROUND: We evaluated the effect of magnesium sulphate on increased pain in 44 patients undergoing staged bilateral total knee arthroplasty (TKA). METHODS: The magnesium group (n=22) and the control group (n=22) received magnesium sulphate and isotonic saline, respectively, throughout the surgery. Postoperative pain (visual analogue scale, VAS) at rest and the amounts of patient-controlled analgesia (PCA, fentanyl) and rescue analgesia (ketoprofen) administered during the first 48 h were compared between the two groups and within each group between the first and second TKA. RESULTS: The VAS scores were significantly higher in the control group than in the magnesium group not only after the first TKA [29 (11) vs 19 (9) at 24 h and 33 (8) vs 24 (10) at 48 h; P=0.001] but also after the second TKA [44 (17) vs 20 (10) at 24 h and 43 (14) vs 25 (10) at 48 h; P<0.001]. In the control group, VAS scores were significantly higher for the second than for the first operated knee [44 (17) vs 29 (11) at 24 h and 43 (14) vs 33 (8) at 48 h; P<0.001 and P=0.006, respectively]. In the magnesium group, there were no significant differences in VAS scores between the first and second TKA. Magnesium significantly reduced the amounts of rescue analgesics and fentanyl administered over the first 48 h postoperatively. CONCLUSIONS: Magnesium sulphate administration significantly reduced postoperative pain and minimized the difference in pain intensity between the first and second operations. CLINICAL TRIAL REGISTRATION: KCT0001361.

Effects of magnesium sulphate on coagulation after laparoscopic colorectal cancer surgery, measured by rotational thromboelastometry (ROTEM® ).

We investigated the effects of magnesium sulphate on blood coagulation profiles using rotational thromboelastometry in patients undergoing laparoscopic colorectal cancer surgery. Patients were randomly allocated to the magnesium group (n = 22) or control group (n = 22). The magnesium group received intravenous magnesium sulphate (50 mg.kg(-1) followed by a continuous infusion of 15 mg.kg(-1) .h(-1) ), whereas the control group received the same volume of isotonic saline. Mean (SD) postoperative serum magnesium levels were 1.60 (0.13) mmol.l(-1) in the magnesium group compared with 0.98 (0.06) mmol.l(-1) in the control group (p < 0.001). All maximum clot firmness values of ROTEM analysis were significantly lower on the third postoperative day in the magnesium group compared with the control group (p < 0.05). We conclude that ROTEM analysis demonstrated that intra-operative administration of intravenous magnesium sulphate reduces blood hypercoagulability in patients undergoing laparoscopic colorectal cancer surgery.

Higher operating tables provide better laryngeal views for tracheal intubation.

BACKGROUND: The present study was conducted to investigate the influence of different operating table heights on the quality of laryngeal view and the discomfort of the anaesthetist during enodotracheal intubation. METHODS: Eight anaesthetists participated, to each of whom 20 patients were allocated. Before induction of anaesthesia, the height of the operating table was adjusted to place the patient's forehead at one of four landmarks on the anaesthetist's body (the order being determined by block randomization with eight blocks): umbilicus (Group U), lowest rib margin (Group R), xiphoid process (Group X), and nipple (Group N). Next, the anaesthetist began the laryngoscopy and evaluated the grade of laryngeal view. For this 'initial posture', the anaesthetist was not allowed to adjust his or her posture (flexion or extension of the neck, lower back, knee, and ankle). This laryngeal view was then re-graded after these constraints were relaxed. At each posture, the anaesthetist's joint movements and discomfort during mask ventilation or intubation were evaluated. RESULTS: The laryngeal view before postural changes was better in Group N than in Group U (P=0.003). The objective and subjective measurements of neck or lower back flexion during intubation were higher in Group U than in Groups X and N (P<0.01 for each). The improvement of laryngeal view resulting from postural changes correlated with the anaesthetist's discomfort score before the postural change (P<0.01). CONCLUSIONS: Higher operating tables (at the xiphoid process and nipple level of the anaesthetist) can provide better laryngeal views with less discomfort during tracheal intubation. TRIAL REGISTRY NUMBER: NCT01649973 (clinicaltrials.gov).

Emergence agitation in children undergoing adenotonsillectomy: a comparison of sevoflurane vs. sevoflurane-remifentanil administration.

BACKGROUND: Sevoflurane is widely used in paediatric anaesthesia but frequently causes emergence agitation (EA). This study evaluated whether limiting the sevoflurane concentration by combining remifentanil with sevoflurane reduced the incidence of EA. METHODS: Eighty-four preschool children scheduled for adenotonsillectomy were randomly assigned to either the remifentanil or sevoflurane group. In the remifentanil group, anaesthesia was induced with thiopental, rocuronium, and 1% sevoflurane. It was maintained with 1% sevoflurane, 60% nitrous oxide in oxygen, and a continuous infusion of remifentanil. For the sevoflurane group, anaesthesia was induced with thiopental, rocuronium, and 8% sevoflurane, and was maintained with 2-3% sevoflurane. Both groups received ketorolac 1 mg/kg and dexamethasone 0.15 mg/kg. EA was measured using the paediatric anaesthesia emergence delirium (PAED) scale and a four-point EA scale in the post-anaesthesia care unit. RESULTS: The scores on the PAED scales were significantly lower in the remifentanil group than in the sevoflurane group [median (interquartile range); 6 (4.25-10.25) vs. 11 (7.75-14.0), P = 0.007], and the proportion of patients with PAED scores ≥ 10 was significantly lower in the remifentanil group than in the sevoflurane group [15 (35.7%) vs. 27 (64.2%), P = 0.009]. The incidence of EA evaluated using the four-point scale was also lower in the remifentanil group [11 (26.1%) vs. 21 (50%), respectively, P = 0.025]. CONCLUSION: The incidence of EA was lower in children undergoing adenotonsillectomy who received a lower concentration of sevoflurane combined with remifentanil than in those given a higher concentration of sevoflurane without remifentanil.

Effects of magnesium sulphate on postoperative coagulation, measured by rotational thromboelastometry (ROTEM(®)).

We investigated the effects of magnesium sulphate on blood coagulation profiles using rotational thromboelastometry in gynaecological patients undergoing pelviscopic surgery. Patients were randomly allocated to the magnesium group (n = 20) or control group (n = 20). The magnesium group received magnesium sulphate (50 mg.kg(-1) followed by continuous infusion of 15 mg.kg(-1).h(-1)), whereas the control group received the same volume of isotonic saline according to the same methods. Mean (SD) postoperative serum magnesium levels were 1.58 (0.17) mmol.l(-1) in the magnesium group compared with 0.98 (0.06) mmol.l(-1) in the control group (p < 0.001). Postoperative clotting time, clot formation time, α-angle and maximum clot firmness of INTEM, and clot formation time, α-angle, and maximum clot firmness of EXTEM were significantly different between the two groups (p < 0.05). Intra-operative infusion of magnesium sulphate seems to attenuate postoperative hypercoagulability by maintaining magnesium levels at the upper limit of the normal range.

Tumor necrosis factor-α and interleukin-1ß expression pathway induced by Streptococcus mutans in macrophage cell line RAW 264.7.

Streptococcus mutans, a major etiological agent of dental caries, frequently causes systemic disease, such as subacute bacterial endocarditis, if it enters the bloodstream. In this study, the production pathways of the proinflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß), induced by S. mutans in mouse macrophage were examined using a quantitative real-time polymerase chain reaction and an enzyme-linked immunosorbent assay. The S. mutans stimulated the expression of TNF-α and IL-1ß mRNA at a multiplicity of infection of 1 : 100, which increased at 2 and 4 h, respectively, to 24 h. It also induced the production of high levels of the TNF-α and IL-1ß proteins, which increased at 2 h and reached a peak at 4 and 24 h, respectively. Nuclear factor-κB (NF-κB) was activated and reached a maximum level 30 min after the S. mutans treatment. The expression of TNF-α and IL-1ß mRNA and protein was suppressed by the treatment with pyrrolidine dithiocarbamate, an NF-κB inhibitor. The S. mutans-induced TNF-α expression was suppressed by the presence of SB203580, a p38 mitogen-activated protein (MAP) kinase inhibitor, or SP600125, a Jun N-terminal kinase (JNK) MAP kinase inhibitor. On the other hand, IL-1ß expression was inhibited by extracellular signal-regulated kinase (ERK)/p38/JNK MAP kinase inhibitor pretreatment. In addition, TNF-α production was suppressed more in the Toll-like receptor 2(-/-) (TLR2(-/-)) macrophages than in the TLR4(-/-) macrophages, whereas IL-1ß production was suppressed more in the TLR4(-/-) macrophages than in the TLR2(-/-) macrophages. These results show that S. mutans stimulates the production of TNF-α and IL-1ß in the mouse macrophage cell line, RAW 264.7, by activating ERK/p38/JNK, and NF-κB through TLR2 and TLR4, respectively.

Drug-administration sequence of target-controlled propofol and remifentanil influences the onset of rocuronium. A double-blind, randomized trial.

BACKGROUND: Remifentanil is known to cause bradycardia and hypotension, as well as the decreases of cardiac output (CO). We hypothesized that hemodynamic suppression by remifentanil would affect the onset time of rocuronium. This study investigated whether the onset of rocuronium was influenced by the drug-administration sequence during induction of anesthesia with target-controlled infusion of propofol and remifentanil. METHODS: Healthy adult patients (n = 126) undergoing elective surgery under general anesthesia were randomized into two groups according to drug-administration sequence. In Remi-Pro-Rocu group (n = 62), remifentanil was infused first, followed by propofol. Then, rocuronium was administered lastly. In Pro-Rocu-Remi group (n = 64), propofol, rocuronium, and remifentanil were given in that order. As a primary outcome, the onset time of rocuronium was measured. Mean arterial pressure (MAP), heart rate (HR), CO, and stroke volume were recorded before anesthesia (T1), at injection of rocuronium (T2), immediately before and after intubation (T3 and T4). RESULTS: In Remi-Pro-Roc group, the onset of rocuronium was delayed significantly compared with Pro-Rocu-Remi group [median (interquartile range); 130 (105-150) vs. 90 (71-100) s, P < 0.001]. At the time of rocuronium injection (T2), MAP, HR, and CO were significantly lower in Remi-Pro-Rocu group than Pro-Rocu-Remi group (P < 0.001). CONCLUSION: The onset time of rocuronium is prolonged significantly by early administration of remifentanil during target-controlled infusion of propofol and remifentanil, and it may be due to the decreased CO caused by remifentanil.

Effects of magnesium sulphate on intraoperative neuromuscular blocking agent requirements and postoperative analgesia in children with cerebral palsy.

BACKGROUND: In this double-blind, randomized, placebo-controlled study, we evaluated the effects of magnesium sulphate on neuromuscular blocking agent requirements and analgesia in children with cerebral palsy (CP). METHODS: We randomly divided 61 children with CP undergoing orthopaedic surgery into two groups. The magnesium group (Group M) received magnesium sulphate 50 mg kg(-1) i.v. as a bolus and 15 mg kg(-1) h(-1) by continuous infusion during the operation. The control group (Group S) received the same amount of isotonic saline. Rocuronium was administered 0.6 mg kg(-1) before intubation and 0.1 mg kg(-1) additionally when train-of-four counts were 2 or more. I.V. fentanyl and ketorolac were used to control postoperative pain. Total infused analgesic volumes and pain scores were evaluated at postoperative 30 min, and at 6, 24, and 48 h. RESULTS: The rocuronium requirement of Group M was significantly less than that of Group S [0.29 (0.12) vs 0.42 (0.16) mg kg(-1) h(-1), P<0.05]. Cumulative analgesic consumption in Group M was significantly less after operation at 24 and 48 h (P<0.05), and pain scores in Group M were lower than in Group S during the entire postoperative period (P<0.05). Serum magnesium concentrations in Group M were higher until 24 h after operation (P<0.05). The incidence of postoperative nausea and vomiting and rescue drug injections was similar in the two groups. No shivering or adverse effects related to hypermagnesaemia were encountered. CONCLUSIONS: I.V. magnesium sulphate reduces rocuronium requirements and postoperative analgesic consumption in children with CP.

I.V. infusion of magnesium sulphate during spinal anaesthesia improves postoperative analgesia.

BACKGROUND: In a randomized, double-blind, prospective study, we have evaluated the effect of i.v. infusion of magnesium sulphate during spinal anaesthesia on postoperative analgesia and postoperative analgesic requirements. METHODS: Forty patients undergoing total hip replacement arthroplasty under spinal anaesthesia were included. After the induction of spinal anaesthesia, the magnesium group (Group M) received magnesium sulphate 50 mg kg(-1) for 15 min and then 15 mg kg(-1) h(-1) by continuous i.v. infusion until the end of surgery. The saline group (Group S) received the same volume of isotonic saline over the same period. After surgery, a patient-controlled analgesia (PCA) device containing morphine and ketorolac was provided for the patients. Postoperative pain scores, PCA consumption, and the incidences of shivering, postoperative nausea, and vomiting were evaluated immediately after surgery, and at 30 min, 4, 24, and 48 h after surgery. Serum magnesium concentrations were checked before the induction of anaesthesia, immediately after surgery, and at 1 and 24 h after surgery. RESULTS: Postoperative pain scores were significantly lower in Group M at 4, 24, and 48 h after surgery (P<0.05). Cumulative postoperative PCA consumptions were also significantly lower in Group M at 4, 24, and 48 h after surgery (P<0.05). Postoperative magnesium concentrations were higher in Group M (P<0.05 at 4, 24, and 48 h after surgery), but no side-effects associated with hypermagnesemia were observed. Haemodynamic variables and the incidences of shivering, nausea, and vomiting were similar in the two groups. CONCLUSIONS: I.V. magnesium sulphate administration during spinal anaesthesia improves postoperative analgesia.

GlideScope video laryngoscope: a randomized clinical trial in 203 paediatric patients.

BACKGROUND: The GlideScope intubating device has been reported to provide a comparable or superior laryngoscopic view compared with direct laryngoscopy in adults. This study compared the use of the GlideScope with direct laryngoscopy for the laryngoscopic view and intubation time in children. METHODS: The laryngoscopic view in 203 children was scored using both the Macintosh laryngoscope and the GlideScope using Cormack and Lehane (C&L) grades. After scoring each laryngoscopic view with and without BURP, the patients were randomly allocated to two groups. The trachea was intubated using direct laryngoscopy (Group DL, n=100) or the GlideScope (Group GS, n=103). We compared C&L grades for the two views in the same patient, and also the time to intubate for each group. RESULTS: The GlideScope improved the view without BURP in the patients with C&L grade 2 (16/26, P<0.01) and with C&L grades 3 and 4 (7/11, P<0.05). The view with BURP was also improved by the GlideScope in C&L grade 2 (4/9, P<0.05) and with C&L grades 3 and 4 (4/5, P=0.059). The mean time for tracheal intubation was 36.0 (17.9) s in the GS group and 23.8 (13.9) s in the DL group (P<0.001). CONCLUSIONS: In children, the GlideScope provided a laryngoscopic view equal to or better than that of direct laryngoscopy but required a longer time for intubation.

Role of signals from the dorsal root ganglion in neuropathic pain in a rat model.

We examined whether signals from the neuroma or the dorsal root ganglion of the injured segment are critical for the generation of neuropathic pain. To this aim, we used a rat model of peripheral neuropathy made by transecting the inferior and superior caudal trunks at the level between the S1 and S2 spinal nerves under enflurane anesthesia. These animals displayed tail-withdrawal responses to normally innocuous mechanical stimulation applied to the tail with a von Frey hair (2 g). Also, these animals, compared to pre-surgical value, displayed shorter tail-withdrawal latencies following immersion of the tail to warm (40 degrees C) or cold (4 degrees C) water. Transection of the S1 spinal nerve between the dorsal root ganglion and neuroma did not change the behavioral signs of neuropathic pain. In contrast, S1 dorsal rhizotomy significantly reduced the behavioral signs. The data suggest that signals arising from the dorsal root ganglion cells of the injured segment, but not from the neuroma, are critical for the generation of neuropathic pain in this model.

Effects of age on behavioral signs of neuropathic pain in an experimental rat model.

The present study examined the effect that aging has on the manifestations of pain behaviors in a rat model of neuropathic pain. Two experiments were conducted. The first experiment compared young, mature and old rats. After tight ligation of the L5 and L6 segmental spinal nerves, young rats displayed much more vigorous behavioral signs of mechanical allodynia and ongoing pain than did either mature or old rats. The second experiment was done using the same rats at two different time points. Spinal nerve ligation was done on the left side of rats when they were young and the same surgery was repeated on the right side 20 weeks later (mature age). Comparison of pain behaviors between the left and right sides confirmed the results of the first experiment. The data suggest that younger rats show much more robust behavioral signs of neuropathic pain compared to older rats.

A behavioral model for peripheral neuropathy produced in rat's tail by inferior caudal trunk injury.

We attempted to develop an experimental animal model using rat's tail for understanding the mechanisms involving peripheral neuropathic pain. Under sodium pentobarbital anesthesia, the left inferior caudal trunk of the rat was resected between the S3 and S4 spinal nerves. Latencies of tail-flick induced by the stimulus such as warm (40 degrees C) and cold (4 degrees C) water to the tail were measured for the following 30 weeks. In addition, sensitivity of the tail to mechanical stimulation was tested with von Frey hairs on these rats. Operated rats showed abnormal sensitivity of the tail to normally innocuous mechanical and thermal (warm and cold) stimuli. We interpreted these results as signs of neuropathic pain following nerve injury. The present model offers several advantages in performing behavioral tests; (1) it is easy to apply thermal stimulation to the rat's tail using a water bottle; (2) it is easy to apply the mechanical stimulation with von Frey hairs and to localize sensitive areas in the tail; and (3) blind behavioral studies are possible due to the lack of deformity in the tail after surgery.