Target-controlled infusion of remimazolam effect-site concentration for total intravenous anesthesia in patients undergoing minimal invasive surgeries.

Background: Although pharmacokinetic and pharmacodynamic models of remimazolam have been developed, their clinical application remains limited. This study aimed to administer a target-controlled infusion (TCI) of remimazolam at the effect-site concentration (Ce) in patients undergoing general anesthesia and to investigate the relationship of the remimazolam Ce with sedative effects and with recovery from general anesthesia. Methods: Fifty patients aged 20-75 years, scheduled for minimally invasive surgery under general anesthesia for less than 2 h, were enrolled. Anesthesia was induced and maintained using Schüttler's model for effect-site TCI of remimazolam. During induction, the remimazolam Ce was increased stepwise, and sedation levels were assessed using the Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale and bispectral index (BIS). Following attainment of MOAA/S scale 1, continuous infusion of remifentanil was commenced, and rocuronium (0.6 mg/kg) was administered for endotracheal intubation. The target Ce of remimazolam and the remifentanil infusion rate were adjusted to maintain a BIS between 40 and 70 and a heart rate within 20% of the baseline value. Approximately 5 min before surgery completion, the target Ce of remimazolam was reduced by 20-30%, and anesthetic infusion ceased at the end of surgery. Nonlinear mixed-effects modeling was employed to develop pharmacodynamic models for each sedation level as well as emergence from anesthesia. Results: The remimazolam Ces associated with 50% probability (Ce50) of reaching MOAA/S scale ≤4, 3, 2, and 1 were 0.302, 0.397, 0.483, and 0.654 µg/mL, respectively. The Ce50 values for recovery of responsiveness (ROR) and endotracheal extubation were 0.368 and 0.345 µg/mL, respectively. The prediction probabilities of Ce and BIS for detecting changes in sedation level were 0.797 and 0.756, respectively. The sedation scale significantly correlated with remimazolam Ce (r = -0.793, P < 0.0001) and BIS (r = 0.914, P < 0.0001). Age significantly correlated with Ce at MOAA/S1 and ROR. Conclusion: Effect-site TCI of remimazolam was successfully performed in patients undergoing general anesthesia. The remimazolam Ce significantly correlated with sedation depth. The Ce50 for MOAA/S scale ≤1 and ROR were determined to be 0.654 and 0.368 µg/mL, respectively.

Effect of total intravenous versus inhalation anesthesia on long-term oncological outcomes in patients undergoing curative resection for early-stage non-small cell lung cancer: a retrospective cohort study.

BACKGROUND: Propofol-based total intravenous anesthesia (TIVA) improves long-term outcomes after cancer surgery compared with inhalation anesthesia. However, its effect on patients undergoing non-small cell lung cancer (NSCLC) surgery remains unclear. We aimed to compare the oncological outcomes of TIVA and inhalation anesthesia after curative resection of early-stage NSCLC. METHODS: We analyzed the medical records of patients diagnosed with stage I or II NSCLC who underwent curative resection at a tertiary university hospital between January 2010 and December 2017. The primary outcomes were recurrence-free survival (RFS) and overall survival (OS) according to anesthesia type. RESULTS: We included 1,508 patients with stage I/II NSCLC. The patients were divided into the TIVA (n = 980) and Inhalation (n = 528) groups. The two groups were well-balanced in terms of baseline clinical characteristics. The TIVA group demonstrated significantly improved RFS (7.7 years, 95% CI [7.37, 8.02]) compared with the Inhalation group (6.8 years, 95% CI [6.30, 7.22], P = 0.003). Similarly, TIVA was superior to inhalation agents with respect to OS (median OS; 8.4 years, 95% CI [8.08, 8.69] vs. 7.3 years, 95% CI [6.81, 7.71]; P < 0.001). Multivariable Cox regression analysis revealed that TIVA was an independent prognostic factor related to recurrence (hazard ratio [HR]: 1.24, 95% CI [1.04, 1.47], P = 0.014) and OS (HR: 1.39, 95% CI [1.12, 1.72], P = 0.002). CONCLUSIONS: Propofol-based TIVA was associated with better RFS and OS than inhalation anesthesia in patients with stage I/II NSCLC who underwent curative resection.

Clinical usefulness of ultrasound as an early diagnostic tool for neuroleukemiosis -a case report.

BACKGROUND: Neuroleukemiosis is a rare complication of leukemia. The diagnosis may be delayed owing to non-specific symptoms and the need for special diagnostic modalities. CASE: A 70-year-old man in his sixth year of remission from acute myeloid leukemia was referred to the pain clinic for shooting and radiating pain in the left posterior leg. A lumbar spine magnetic resonance imaging showed mild disc bulging of the L2-3, which was insufficient to explain the patient's symptoms. With insufficient pain response to lumbar epidural block and piriformis injection, we examined both sciatic nerves using an ultrasound and identified an enlarged hypoechoic mass on the left sciatic nerve at mid-thigh level. After that, we biopsied the mass under general anesthesia, and histology confirmed it to be neuroleukemiosis. CONCLUSIONS: Ultrasound is an inexpensive, non-invasive, simple, and quick diagnostic modality that can be used as a screening tool in the diagnosis of neuroleukemiosis.

Acute mental change as the presenting sign of posthepatectomy hepatic failure: A case report.

RATIONALE: Hepatectomy is a treatment to increase survival and curability of patients with intrahepatic lesions or malignant tumors. However, posthepatectomy liver failure (PHLF) can occur. This case is a patient showing acute mental change in postanesthetic care unit (PACU) as an uncommon symptom of PHLF after extended right hepatectomy. PATIENT CONCERNS: A 68-year-old male patient was admitted for surgery of Klatskin tumor. He had hypertension and atrial fibrillation. His model for end-stage liver disease score was 16 pts. His serum bilirubin and ammonia levels were 4.75 mg/dL and 132.8 mcg/dL, respectively. Other laboratory data were nonspecific. He underwent extended right hepatic lobectomy including segments IV-VIII for 9 hours. Weight of liver specimen was 1028 g which was about 58% of total liver volume based on computed tomographic volumetry. The patient was extubated and moved to the PACU with stable vital sign and regular self-breathing. He could obey verbal commands. Fifteen minutes after admission to the PACU, the patient showed abruptly decreasing mental status and self-breathing. DIAGNOSES: Brain computed tomography, blood culture, and sputum culture were performed to diagnose brain lesions and sepsis for evaluating the sudden onset comatous mental status. Results showed nonspecific finding. INTERVENTIONS: He was intubated for securing airway and applying ventilatory care. The patient was moved to the intensive care unit. He received intensive conservative therapy including continuous renal replacement therapy and broad-spectrum antibiotics. OUTCOMES: The patient's condition was worsened. He expired on postoperative day 3. LESSONS: Acute mental change is uncommon and rare as initial symptoms of PHLF. Therefore, clinician may overlook the diagnosis of PHLF in patients with acute mental change after hepatectomy. Thus, clinician should plan an aggressive treatment for PHLF including liver transplantation by recognizing any suspicious symptom, although such symptom is rare.

Ischemic time of graft liver forces Th1-to-Th2 activity toward Th1 activity in patients who underwent living donor liver transplantation.

Recipient's immune responses are an important factor in allograft survival in transplantation. Cytokines are reflected with immune responses. In the present study, we aimed to evaluate potential affecting factors of liver allograft survival and their possible correlation with seroum cytokine levels in living donor liver transplantation (LDLT). One hundred and seventy-one adult patients' data were collected retrospectively. Five cytokines were collected: interferon (IFN)-γ, interleukin (IL)-2, IL-10, IL-6, and IL-17. Ischemic time of liver grafts was divided into two periods: cold and warm ischemic times (CIT and WIT, respectively). CIT had no statically significant correlation, but WIT showed a significant correlation with IFN-γ, IL-2, and IL-17 serum levels (r = 0.0252, 0.282, 0.178, respectively; P < 0.05). WIT was dichotomized as T1 (<22 min), T2 (22-70 min), and T3 (>70 min). IFN-γ was significantly increased in T2 and T3 as compared to T1. IL-6 was in T3 compared to T1 and T2. IL-17 was in T3 compared to T1. For the Th1-to-Th2 ratio, IFN-γ/IL-10, IFN-γ/IL-6, and IL-2/IL-10 were significantly different in T2 and T3 as compared to T1, and also in T3 as compared to T2. Th1 cell activities were enhanced with increased WIT. In conclusion, the longer WIT (>70 min) in LDLT is more likely to induce immunological reactions of recipients by leading to a deleterious cytokine balances in favor of an reinforced production of Th1 cytokines.

Compression stockings reduce the incidence of hypotension but not that of cerebral desaturation events in the beach-chair position: a randomized controlled trial.

BACKGROUND: The beach-chair position (BCP) results in decreases in venous return, cardiac output, and cerebral perfusion pressure. In this randomized, prospective study, we investigated whether applying thigh-high compression stockings affected the maintenance of regional cerebral tissue oxygen saturation (rSO2) in the BCP. METHODS: Patients undergoing orthopedic surgery in the BCP under general anesthesia were included and assigned randomly to the control or the compression stocking group. Appropriately sized thigh-high compression stockings were applied to the patients in the stockings group. All patients were tilted, up to 45°, throughout the operation. Non-invasive blood pressure, invasive arterial blood pressure zeroed at the external auditory meatus, and rSO2 were recorded. RESULTS: Data were analyzed from 19 patients per group. In the BCP, the values of rSO2 and blood pressure decreased significantly compared with those at baseline, with no significant difference between the groups. The incidences of cerebral desaturation events (CDEs) were similar between the groups; however, that of hypotension was significantly lower in the compression stocking group. During 36 CDEs, the levels of rSO2 and blood pressure decreased significantly compared with those at baseline in both groups. No significant correlation was found between rSO2 and blood pressure. CONCLUSIONS: Thigh-high compression stockings reduced the incidence of hypotension but not that of CDEs. Our results suggest that other factors, beyond hypotension itself, contribute to CDEs and in other words, efforts just to reduce the incidence of hypotension may not mainly contribute to a reduction of CDEs occurrence in the BCP under general anesthesia.

Effects of Macrolide and Corticosteroid in Neutrophilic Asthma Mouse Model.

BACKGROUND: Asthma is a disease of chronic airway inflammation with heterogeneous features. Neutrophilic asthma is corticosteroid-insensitive asthma related to absence or suppression of TH2 process and increased TH1 and/or TH17 process. Macrolides are immunomodulatory drug that reduce airway inflammation, but their role in asthma is not fully known. The purpose of this study was to evaluate the role of macrolides in neutrophilic asthma and compare their effects with those of corticosteroids. METHODS: C57BL/6 female mice were sensitized with ovalbumin (OVA) and lipopolysaccharides (LPS). Clarithromycin (CAM) and/or dexamethasone (DXM) were administered at days 14, 15, 21, 22, and 23. At day 24, the mice were sacrificed. RESULTS: Airway resistance in the OVA+LPS exposed mice was elevated but was more attenuated after treatment with CAM+DXM compared with the monotherapy group (p<0.05 and p<0.01). In bronchoalveolar lavage fluid study, total cells and neutrophil counts in OVA+LPS mice were elevated but decreased after CAM+DXM treatment. In hematoxylin and eosin stain, the CAM+DXM-treated group showed less inflammation additively than the monotherapy group. There was less total protein, interleukin 17 (IL-17), interferon γ, and tumor necrosis factor α in the CAM+DXM group than in the monotherapy group (p<0.001, p<0.05, and p<0.001). More histone deacetylase 2 (HDAC2) activity was recovered in the DXM and CAM+DXM challenged groups than in the control group (p<0.05). CONCLUSION: Decreased IL-17 and recovered relative HDAC2 activity correlated with airway resistance and inflammation in a neutrophilic asthma mouse model. This result suggests macrolides as a potential corticosteroid-sparing agent in neutrophilic asthma.

Combined Spinal Cord Stimulation and Peripheral Nerve Stimulation for Brachial Plexopathy: A Case Report.

Brachial plexopathy usually results from an iatrogenic brachial plexus injury and can sometimes cause severe chronic pain and disability. There are a number of possible treatments for this condition, including medication, physical therapy, nerve blocks, and neuromodulation, but they are not always successful. Recently, combined spinal cord stimulation (SCS) and peripheral nerve stimulation (PNS) have been tried for various chronic pain diseases because of their different mechanisms of action.Here, we describe the case of a 54-year-old man who was diagnosed with brachial plexopathy 8 years ago. He underwent video-assisted thoracoscopic surgery to remove a superior mediastinal mass. However, his brachial plexus was damaged during the surgery. Although he had received various treatments, the pain did not improve. For the management of intractable severe pain, he underwent SCS 2 years ago, which initially reduced his pain from numeric rating scale (NRS) 10/10 to NRS 4 - 5/10, but the pain then gradually increased, reaching NRS 8/10, 6 months ago. At that time, he was refractory to other treatments, and we therefore applied PNS in combination with SCS. The PNS electrode was positioned on the radial nerve under ultrasound guidance. After combined PNS and SCS, his background pain disappeared, although a breakthrough pain (NRS 3 - 4/10) was caused intermittently by light touch. Furthermore, the patient's need for analgesics decreased, and he was satisfied with the outcome of this combined treatment. We concluded that combined SCS and PNS is a very useful treatment modality, which can stimulate the target nerve both directly and indirectly, and hence, relieve pain from brachial plexopathy.

Percutaneous adjustment method for transversely migrated spinal cord stimulation leads: a technical report.

Lead migration is the most common complication of spinal cord stimulation (SCS). However, the only corrective method for lead migration is revision surgery, which may cause additional complications. Here, we describe a new technique for adjusting a transversely migrated SCS lead. The medical records of four patients diagnosed with complex regional pain syndrome (n = 3) or failed back surgery syndrome (n = 1) who underwent implantation of percutaneous leads for SCS were retrospectively reviewed. Transverse lead migration was diagnosed radiographically after patients reported recurrence of pain or numbness in treated sites. The guide wire from the SCS implant kit was bent and inserted into the target epidural space using a 14-gauge Tuohy needle. When the guide wire contacted the migrated SCS lead, they were advanced to the correct location under C-arm guidance. After re-adjustment of the SCS lead, good coverage of the electrical stimulation was confirmed. Patients were followed for 9-19 months and they reported satisfactory pain relief and good electrical coverage after adjusting the SCS lead. Here, we describe a new technique for adjusting a transversely migrated SCS lead using a percutaneous epidural approach as a simple, safe, and cost-effective alternative to revision surgery.

Pulsed radiofrequency under ultrasound guidance for the tarsal tunnel syndrome: two case reports.

Tarsal tunnel syndrome (TTS) is a compression neuropathy that results from entrapment of the posterior tibial nerve or its branches. TTS may be treated either by conservative measures, including physical therapy, medications, and steroid injections, or by surgical decompression. Despite a variety of treatments, a few cases of TTS will relapse, and many cases of recurrent TTS will require re-operation. Pulsed radiofrequency (PRF) is known to have a number of advantages for pain management, particularly as this technique does not cause neural compromise such as motor weakness. Here, we report a new application of ultrasound-guided PRF in two cases of intractable TTS. Both patients had a long duration of severe foot pain and had been treated with various therapeutic modalities without lasting relief. We applied ultrasound-guided PRF to the affected posterior tibial nerve in each patient, and both had significantly reduced pain intensity scores and analgesic requirements without any complications. Ultrasound-guided PRF for intractable TTS relieved severe foot pain. It may supersede surgery as a reliable treatment for intractable TTS.

Prediction of early allograft dysfunction using serum phosphorus level in living donor liver transplantation.

Serum phosphorus is greatly affected by liver surgeries, but its change after liver transplantation has not yet been clarified. We investigated the predictive role of serum phosphorus for early allograft dysfunction (EAD) after living donor liver transplantation (LDLT). Perioperative factors, including serum phosphorus level, of 304 patients who underwent LDLT were retrospectively studied and compared between patients with and without EAD after LDLT. Potentially significant factors (P < 0.15) in univariate comparisons were subjected to multivariate logistic regression analysis to develop a prediction model for EAD. A total of 48 patients (15.8%) met the EAD criteria. Patients with EAD experienced more severe preoperative disease conditions, higher one-month mortality and more elevated serum phosphorus concentrations during the first week after surgery compared with patients without EAD (P = 0.016). Multivariate analysis showed that a serum phosphorus level ≥4.5 mg/dl on postoperative day 2 was an independent predictor of EAD occurrence after LDLT (relative risk: 2.36, 95% confidence interval [1.18-4.31], P = 0.017), together with a history of past abdominal surgery, emergency transplantation and preoperative continuous veno-venous haemodiafiltration. These data indicate that hyperphosphataemia during the immediate postoperative days could be utilized as a predictor of EAD after LDLT.

Sugammadex versus neostigmine reversal of moderate rocuronium-induced neuromuscular blockade in Korean patients.

BACKGROUND: Rapid and complete reversal of neuromuscular blockade (NMB) is desirable at the end of surgery. Sugammadex reverses rocuronium-induced NMB by encapsulation. It is well tolerated in Caucasian patients, providing rapid reversal of moderate (reappearance of T2) rocuronium-induced NMB. We investigated the efficacy and safety of sugammadex versus neostigmine in Korean patients. METHODS: This randomized, safety assessor-blinded trial (NCT01050543) included Korean patients undergoing general anesthesia. Rocuronium 0.6 mg/kg was given prior to intubation with maintenance doses of 0.1-0.2 mg/kg as required. Patients received sugammadex 2.0 mg/kg or neostigmine 50 µg/kg with glycopyrrolate 10 µg/kg to reverse the NMB at the reappearance of T2, after the last rocuronium dose. The primary efficacy endpoint was the time from sugammadex or neostigmine administration to recovery of the train-of-four (TOF) ratio to 0.9. The safety of these medications was also assessed. RESULTS: Of 128 randomized patients, 118 had evaluable data (n = 59 in each group). The geometric mean (95% confidence interval) time to recovery of the TOF ratio to 0.9 was 1.8 (1.6, 2.0) minutes in the sugammadex group and 14.8 (12.4, 17.6) minutes in the neostigmine group (P < 0.0001). Sugammadex was generally well tolerated, with no evidence of residual or recurrence of NMB; four patients in the neostigmine group reported adverse events possibly indicative of inadequate NMB reversal. CONCLUSIONS: Sugammadex was well tolerated and provided rapid reversal of moderate rocuronium-induced NMB in Korean patients, with a recovery time 8.1 times faster than neostigmine. These results are consistent with those reported for Caucasian patients.

Amnesia and pain relief after cardiopulmonary resuscitation in a cancer pain patient: a case report.

The mechanism of chronic pain is very complicated. Memory, pain, and opioid dependence appear to share common mechanism, including synaptic plasticity, and anatomical structures. A 48-yr-old woman with severe pain caused by bone metastasis of breast cancer received epidural block. After local anesthetics were injected, she had a seizure and then went into cardiac arrest. Following cardiopulmonary resuscitation, her cardiac rhythm returned to normal, but her memory had disappeared. Also, her excruciating pain and opioid dependence had disappeared. This complication, although uncommon, gives us a lot to think about a role of memory for chronic pain and opioid dependence.

Post-traumatic Back Pain Revealed as Tuberculous Spondylitis -A Case Report-.

Tuberculous spondylitis is a very rare disease, but it can result in bone destruction, kyphotic deformity, spinal instability, and neurologic complications unless early diagnosis and proper management are done. Because the most common symptom of tuberculous spondylitis is back pain, it can often be misdiagnosed. Atypical tuberculous spondylitis can be presented as a metastatic cancer or a primary vertebral tumor. We must make a differential diagnosis through adequate biopsy. A 30-year-old man visited our clinic due to back and chest pain after a recent traffic accident. About 1 year ago, he had successfully recovered from tuberculous pleurisy after taking anti-tuberculosis medication. We performed epidural and intercostal blocks but the pain was not relieved. For the further evaluation, several imaging and laboratory tests were done. Finally, we confirmed tuberculous spondylitis diagnosis with the biopsy results.

The effect of ulinastatin on hemostasis in major orthopedic surgery.

BACKGROUND: Ulinastatin, a urinary trypsin inhibitor, is widely used to treat acute systemic inflammatory disorders. However, the effects of ulinastatin, especially on the potential for hemostasis, have not been fully elucidated. This study examined whether ulinastatin had any beneficial effects on blood loss and blood transfusion requirements in patients undergoing major orthopedic surgery. METHODS: Eighty patients, aged 18 to 75 years, scheduled for major orthopedic surgery were enrolled in this study and were divided into the ulinastatin (n = 40) and control (n = 40) groups. Following the induction of general anesthesia, and immediately before the surgical incision, the patients in the ulinastatin group were given 5,000 units/kg of ulinastatin, which were mixed in 100 ml normal saline intravenously over 30 min, while those in the control group received the same volume of normal saline. The amounts of blood loss, infused fluid, and transfused blood products were measured throughout the study period. Blood samples for coagulation parameters were obtained before inducing anesthesia (T1), at the end of surgery (T2), and 12 h after surgery (T3). RESULTS: The amounts of blood loss and infused fluid during surgery were not significantly different between the two groups. However, 12 h postoperative blood loss was significantly less in the ulinastatin group than in the control group (255.0 +/- 133.2 ml VS. 395.4 +/- 338.4 ml, P < 0.05). CONCLUSIONS: Our data suggest that a single infusion of ulinastatin in major orthopedic surgery is associated with decreased blood loss in the early postoperative period.