Video versus ultrasound pupillometry for detecting increased pupillary diameters due to nociceptive stimuli: a prospective observational study.

PURPOSE: Ultrasound pupillometry (UP) is a potential alternative to video pupillometry (VP) for assessing changes in patients' pupillary diameter (ΔPD) due to surgical nociception, but the reproducibility of UP and VP has been unclear. We evaluated the reproducibility of nociceptive ΔPD measured with both methods. SUBJECTS AND METHODS: This prospective observational trial with 15 healthy volunteers aged ≥ 18 years was conducted at a Japanese teaching hospital. The ΔPD due to tetanic stimuli randomly applied at 10-60 mA was measured with VP and UP. The primary outcome was the correlation between the ΔPD measured with VP and that measured with UP. The secondary outcome was the agreement between the methods. We also evaluated ΔPD pattern changes due to the raised pain intensity in each method. RESULTS: The noxious ΔPD values of UP were weakly but significantly correlated with those of VP (Spearman's ρ = 0.38, p < 0.001). A significant constant error was identified between the two measurements (Bland-Altman: mean of the difference in ΔPD (VP - UP), - 0.4 [95% CI: - 0.52 to - 0.28, p < 0.001], generalized estimating equation: a beta estimator of ΔPD: 0.41, [95% CI: 0.26-0.56, p < 0.001]). The ΔPD pattern changes due to the raised tetanic stimuli were almost the same in the two methods. CONCLUSION: Due to the significant constant error, we consider the reproducibility of the measured ΔPD between UP and VP moderate. Trial registry number UMIN 000047145. Prior to the subjects' enrollment, the trial was registered with the University Hospital Medical Information Network (Principal investigator: Mao Konno, Date of registration: 3.11.2022). https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000053778 .

Ketamine Does Not Change Natural Killer Cell Cytotoxicity in Patients Undergoing Cancer Surgery: Basic Experiment and Clinical Trial.

Background: The natural killer cell cytotoxicity (NKCC) suppressed by nociceptive stimuli, systemic inflammation, and drugs used during cancer surgery may be associated with poor outcomes. We investigated the potential modulation of ketamine on NKCC in vitro and in a clinical setting during cancer surgery. Subjects and Methods. The NK cell line KHYG1 was cultured for the in vitro experiments. The NK cells were treated with 3 and 10 µM ketamine (the ketamine groups) or without ketamine (the control) for 4, 24, and 48 h. The posttreatment NKCC was measured with a lactate dehydrogenase assay and compared among the treatment groups. For the clinical study, lung cancer patients (n = 38) and prostate cancer patients (n = 60) who underwent radical cancer surgeries at a teaching hospital were recruited. The patients received propofol and remifentanil superposed with or without ketamine (ketamine group, n = 47; control group, n = 51). The primary outcome was the difference in NKCC between these groups. Results: In the in vitro experiment, the cytotoxicity of NK cells was similar with or without ketamine at all of the incubation periods. The patients' NKCC was also not significantly different between the patients who received ketamine and those who did not, at the baseline (36.6 ± 16.7% vs. 38.5 ± 15.4%, p = 0.56) and at 24 h (25.6 ± 12.9% vs. 27.7 ± 13.5%, respectively, p = 0.49). Conclusion: Ketamine does not change NKCC in vitro or in the clinical setting of patients who undergo cancer surgery. This trial is registered with UMIN000021231.

Moderate rate of implementation of spinal anesthesia for cesarean section: does it improve neonatal well-being? A case-control study.

Before 2013, almost none of the cesarean section (CS) deliveries at our institution were performed with spinal anesthesia (SA), but after 2013 SA became the first-choice anesthesia for CS because it achieved better neonatal outcomes. However, the current rate of SA implementation at our institution was estimated to be approx. 60-70%, which is intermediate between these at other institutions in Japan or in other countries. This raises a question: What rate of SA use among CS cases achieves the best neonatal outcomes? To answer this question, we conducted this single-center case-control study with 1326 CS cases between 1994 and 2017 and compared the neonatal outcomes before to those after 2013. The logistic regression models were prepared to estimate the risk of birth asphyxia defined as a 5-min Apgar of < 7, associated with eight potential confounders, including the modified anesthetic protocol. The modified protocol was not a significant independent factor for neonatal asphyxia, indicating that our moderate SA priority protocol did not improve the neonatal outcomes even when compared to the outcomes at a 0% SA rate. A > 70% rate of SA implementation may be needed to provide better neonatal outcomes.

Immunomodulation by ketamine as an adjunct to total intravenous anesthesia in patients undergoing minimally invasive radical prostatectomy: A randomized pilot trial.

Post-surgery immunomodulation, including reduced natural killer cell cytotoxicity (NKCC), is recognized as a predictor of poor outcomes in patients following cancer surgery. The present study investigated direct immunomodulation via ketamine as an anesthetic adjuvant in patients undergoing cancer surgery. The present non-double blinded randomized trial was conducted at Hirosaki University Hospital with 60 patients who underwent minimally invasive robotic radical prostatectomy to minimize the immunomodulation due to surgical stress. Patients received total intravenous anesthesia using propofol and remifentanil, with ketamine as an anesthetic adjuvant (the ketamine group) or without ketamine (the control group). The primary outcome was the difference in NKCC between these groups. The secondary outcomes were the differences in neutrophil-lymphocyte ratio (NLR) and levels of interleukin (IL)-6, IL-1ß, IL-10 and tumor necrosis factor-alpha (TNF-α). NKCC and cytokines were measured before anesthesia (baseline) and at 6 and 24 h after baseline measurements were recorded. NLR was determined on the last day before admission and at 48 h post-baseline. NKCC values were similar in each group at 6 h when compared with respective baseline results (baseline control, 36.9±15.6%; 6 h control, 38.3±13.4%; baseline ketamine, 36.1±17.0%; 6 h ketamine, 36.6±16.4%) but significantly decreased at 24 h (control, 26.5±12.2%; ketamine, 24.1±12.7%; P<0.001). There were no significant differences in NKCC between the ketamine and control groups (P=0.64) at any of the assessed time points. NLR, IL-1ß, IL-10 and TNF-α levels were also similar between two groups. In contrast, IL-6 at 24 h was significantly lower in the ketamine group compared with the control group (mean difference, -7.3 pg ml-1; 95% confidence interval, -14.4 to -0.2; P=0.04). Ketamine as an anesthetic adjuvant did not provide direct immunomodulation in patients who underwent cancer surgery.

Can tissue dielectric constant measurements assess circulating blood volume changes in patients undergoing haemodialysis?

BACKGROUND: The tissue dielectric constant (TDC) method uses an open-ended coaxial probe to achieve non-invasive measurement of water content in skin. The aim of our study was to test the hypothesis that the changes in circulating blood volume would be associated with the changes in TDC values in patients undergoing haemodialysis. METHODS: In this prospective descriptive study, TDC measurements were performed for three parts of the body (the face, shin and hand) before and after patients underwent haemodialysis (N = 83). The primary outcome measure was the correlation between the amount of water removal and ΔTDC at each body site measured (ΔTDC = posthaemodialysis TDC-prehaemodialysis TDC). The secondary outcome measure was the mean difference in TDC value before and after haemodialysis. RESULTS: The TDC values measured at each part of the body were significantly reduced after haemodialysis, but the percentage difference between pre- haemodialysis and posthaemodialysis was small for the face, shin and hand, with %mean ± SE values of -4.4 ± 0.70, -3.2 ± 0.98 and -6.0 ± 1.6; 95 per cent confidence intervals (lower bound to upper bound) of 3.0-5.8, 1.3-5.2 and 2.7-9.2; and P values of P = 0.000, P = 0.000 and P = 0.000, respectively. The inverse correlation between ΔTDC and the amount of water removal was also weak (correlation at the face, r = -0.25, P = 0.028; at the shin, r = -0.26, P = 0.018; and at the hand, no significant correlation). CONCLUSION: Our results indicate that TDC measurement can be used to assess the changes in local oedema, but may be unlikely to evaluate real-time changes in the circulating blood volume in a clinical setting.

Ketamine suppresses the proliferation of rat C6 glioma cells.

The present study investigated the effects of N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine, on the growth of gliomas. To analyze the effects of ketamine treatment, rat C6 glioma cells arising from astrocytes, and RNB cells representing non-malignant astrocytes, were examined. In ketamine-treated C6 cells, the gene expression changes associated with cell proliferation following ketamine treatment were evaluated using a cDNA microarray. A cell proliferation assay was performed to analyze the dose-dependent proliferation of C6 glioma and RNB cells following culture (72 h) with ketamine treatment (0-100 µM). Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays were performed following cell incubation with/without ketamine, to confirm if the ketamine-induced cell death of C6 glioma and RNB cells were due to apoptosis. In addition, cell proliferation and TUNEL assays were performed following cell incubations with a selective NMDAR antagonist, D-2-amino-5-phosphonovaleric acid (D-AP5). Analysis of the cDNA microarray indicated that the growth of C6 glioma cells were suppressed by the effects of ketamine. Furthermore, results of the proliferation assay confirmed that ketamine treatment inhibited C6 cell proliferation, most notably at a dose of 30 µM (n=7, 66.4%; P<0.001). The TUNEL assay results revealed that ketamine induced an apoptotic effect on C6 glioma cells, with a significant effect on the rate of death observed at all tested concentrations (3, 10, 30 and 100 µM). Results of the aforementioned proliferation and TUNEL assay experiments were reproduced when ketamine was replaced with a selective NMDAR antagonist, D-AP5. However, the NMDARantagonist-induced effects were not observed in RNB cell cultures. Although it would be premature to apply the results from the present study to human cases, these results indicated that ketamine is an anesthetic candidate providing potential benefit for glioma resection.

Pilot Study of Changes in Presepsin Concentrations Compared With Changes in Procalcitonin and C-Reactive Protein Concentrations After Cardiovascular Surgery.

OBJECTIVE: The authors investigated the presepsin-concentration profile after cardiac surgery compared with those of procalcitonin (PCT) and C-reactive protein (CRP). DESIGN: A single-center, prospective, observational clinical study. SETTING: Hirosaki University Hospital. PARTICIPANTS: Patients who underwent cardiovascular surgery without preoperative infection and end-stage kidney disease requiring dialysis. The patients also were subdivided into 2 groups with respect to the use of cardiopulmonary bypass (CPB). MEASUREMENTS AND MAIN RESULTS: Presepsin, PCT, and CRP were measured 4 times: before the induction of anesthesia (baseline), postoperative day (POD) 0, POD 1, and POD 2. Data are expressed as median (25th, 75th interquartiles). A total of 33 patients were examined: 22 patients with CPB and 11 without CPB. For the entire patient series, the presepsin concentrations on POD 0 (220 [166-445] pg/mL), POD 1 (328 [210-581] pg/mL), and POD 2 (310 [202-368] pg/mL) were increased significantly (p < 0.05) compared with baseline (176 [123-275] pg/mL). The PCT and CRP concentrations on POD 1 (0.57 [0.27-1.29] ng/mL and 5.4 [3.1-8.8] mg/dL) and POD 2 (0.64 [0.33-1.43] ng/mL and 11.8 [4.4-17.0] mg/dL) also were increased significantly (p < 0.05) compared with baseline (0.04 [0.03-0.06] ng/mL and 0.07 [0.03-0.22] mg/dL). However, the median concentrations of presepsin up to POD 2 were less than the reported cut-off value (600 pg/mL) to detect infections, whereas those of PCT were above the reported cut-off value (0.5 ng/mL). The increases in presepsin and PCT concentrations were independent of the use of CPB. CONCLUSIONS: Cardiovascular surgery significantly increased presepsin concentrations, earlier than PCT and CRP.

A case report of sudden thrombocytopenia detected only by in vitro analysis.

We experienced an unexpected thrombocytopenia detected only in vitro during radical prostatectomy for a 66-year-old patient. Thrombocytopenia with platelet aggregation was observed in a blood sample obtained using a heparinized syringe (not by ethylene diamine tetra-acetic acid tube). Although we could not exclude platelet agglutination in vivo, no thrombosis or coagulation disorder was observed. We changed the anti-coagulant in the arterial catheter carrier fluid (saline) from heparin to argatroban, and continued with the operation. No embolic complications were observed during the perioperative period. Although pseudothrombocytopenia or heparin-induced thrombocytopenia was highly suspected in the present case, we were not able to confirm which of the two developed. Multi-directional attention and care may be required for perioperative unexpected thrombocytopenia.

Ketamine and propofol have opposite effects on postanesthetic sleep architecture in rats: relevance to the endogenous sleep-wakefulness substances orexin and melanin-concentrating hormone.

BACKGROUND: Anesthesia and surgery disturb sleep. Disturbed sleep adversely affects postoperative complications involving the cardiovascular system, diabetes, and infection. General anesthetics share neuronal mechanisms involving endogenous sleep-wakefulness-related substances, such as orexin (OX) and melanin-concentrating hormone (MCH). We evaluated changes in sleep architecture and the concentration of OX and MCH during the peri-anesthetic period. METHODS: To examine sleep architecture, male Sprague-Dawley rats weighing 350-450 g received ketamine 100 mg/kg (n = 9) or propofol 80 mg/kg (n = 6) by intraperitoneal injection. Electroencephalography was recorded from 2 days pre- to 5 days postanesthesia. To quantify levels of OX and MCH, 144 similar rats received the same doses of ketamine (n = 80) or propofol (n = 64). Brain concentrations of these substances were determined at 0, 20, 60, and 120 min after anesthetic administration. RESULTS: Ketamine decreased OX content in the hypothalamus during the anesthesia period. OX content was restored to pre-anesthesia levels in the hypothalamus and pons. Both anesthetics increased brain MCH content in the postanesthetic period, with the degree of increase being greater with propofol. Ketamine enhanced wakefulness and inhibited non-rapid eye movement sleep (NREMS) immediately after anesthesia. Conversely, propofol inhibited wakefulness and enhanced NREMS in that period. Ketamine inhibited wakefulness and enhanced NREMS during the dark phase on the first postanesthesia day. CONCLUSIONS: Anesthetics affect various endogenous sleep-wakefulness-related substances; however, the modulation pattern may depend on the type of anesthetic. The process of postanesthetic sleep disturbance was agent specific. Our results provide fundamental evidence to treat anesthetic-related sleep disturbance.

Rethinking general anesthesia for cesarean section.

In this review, we describe the current consensus surrounding general anesthetic management for cesarean section. For induction of anesthesia, rapid-sequence induction using thiopental and suxamethonium has been the recommended standard for a long time. In recent years, induction of anesthesia using propofol, rocuronium, and remifentanil have been gaining popularity. To prevent aspiration pneumonia, a prolonged preoperative fasting and an application of cricoid pressure during induction of anesthesia have been recommended, but these practices may require revision. Guidelines for difficult airway management were developed first in obstetric anesthesia, and the use of a supraglottic airway is now recognized as an effective rescue device. After the delivery of a fetus, switching from volatile anesthetics to intravenous anesthetics has been recommended to avoid uterine atony. At the same time, intraoperative awareness should be avoided. The rate of persistent wound pain is higher when only general anesthesia was used during cesarean section than with regional anesthesia, and thus it is necessary to provide a sufficient postoperative analgesia using multimodal analgesia, including intravenous patient-controlled analgesia (IV-PCA), transversus abdominis plane (TAP) block, non-steroidal inflammatory drugs, and acetaminophen.

Endogenous neuropeptide S tone influences sleep-wake rhythm in rats.

Neuropeptide S (NPS) is an endogenous peptide that exerts wakefulness promoting, analgesic, and anxiolytic effects when administered exogenously. However, it remains to be determined if endogenous NPS tone is involved in the control of the diurnal sleep-wake cycle, or spontanous behavior. In this study, we examined the effects of the NPS receptor antagonist [D-Cys((t)Bu)(5)]NPS (2 and 20 nmol, icv) on physiological sleep and spontaneous locomotor behavior. The higher dose of [D-Cys((t)Bu)(5)]NPS decreased the amount of time spent in wakefulness [control 782.5 ± 25.5 min, treatment 751.7 ± 28.1 min; p<0.05] and increased the time spent in NREMS [control 572.6 ± 17.2 min, treatment 600.2 ± 26.1 min; p<0.05]. There was no statistically significant difference in time spent in REMS. There were no behavioral changes including abnormal gross motor behavior in response to [D-Cys((t)Bu)(5)]NPS administration. Collectively these data suggest an involvement of the endogenous NPS/NPS receptor system in physiological sleep architecture.

[Analgesic efficacy and clinical safety of intraperitoneal instillation combined with rectus sheath block using ropivacaine for pain relief after laparoscopic gynecological surgery].

BACKGROUND: The aim of this study was to evaluate the analgesic efficacy and safety of rectus sheath block combined with intraperitoneal instillation using two doses of ropivacaine in patients undergoing laparoscopic gynecological surgery. METHODS: Altogether 53 consenting women were randomized to receive intraperitoneal infiltration with 0.25% ropivacaine or 0.5% ropivacaine followed by rectus sheath block with 0.375% ropivacaine. The outcomes of clinical safety were measured using plasma concentration of local anesthetics and occurrence of toxic symptoms. The analgesic efficacy was assessed using numerical rating scales for pain and morphine consumption up to 24 hours after surgery. RESULTS: Patients' baseline characteristics, surgical factors, and analgesic outcomes were comparable between the two groups. Although peak plasma concentration of ropivacaine was significantly higher in patients receiving 0.5% ropivacaine, none of analyzed concentrations was above the toxic ones. Besides, no patients showed any symptoms of local anesthetic toxicity. CONCLUSIONS: The present study showed that the combination of rectus sheath block with intraperitoneal instillation of ropivacaine was safe and potent enough to relieve pain after laparoscopic surgery.

Can anesthetic techniques or drugs affect cancer recurrence in patients undergoing cancer surgery?

Despite the development of effective chemotherapy and radiotherapy, surgery remains the mainstay treatment of many cancers, requiring anesthesia. Almost all cancer deaths after primary surgery are attributable to recurrence or metastases. Recently it has been hypothesized that the perioperative anesthetic management of cancer patients could potentially affect the risk of recurrence and metastases, which implies a key role for anesthesiologists in choosing anesthetic agents and techniques that optimize the balance between the metastatic potential of the tumor versus its elimination by antimetastatic immune defenses. This review summarizes available experimental information on the potential effects of common anesthetic agents and techniques on cancer metastases and the conflicting retrospective clinical data on regional anesthesia in various types of cancer. A number of prospective, randomized, multicenter, clinical trials are in progress, and their results are eagerly awaited.

Effects of oral rehydration therapy on gastric volume and pH in patients with preanesthetic H2 antagonist.

Recent preanesthetic fasting practice allows patients to take clear fluids up to 2 h before surgery without taking any antacid for the prophylaxis of aspiration pneumonia; this practice is defined as oral rehydration therapy (ORT). It has been reported that with ORT the gastric volume may be significantly lower than that with a standard fasting regimen, although in a standard fasting regimen without preanesthetic antacid, gastric pH and volume values could be critical for causing aspiration pneumonia. In this study we compared gastric fluid status in patients with ORT and those with a standard fasting regimen; patients in both groups received a preanesthetic H(2) antagonist. One hundred and four patients were randomly assigned to either the ORT or standard fasting group, and all were given roxatidine 75 mg 2 h before surgery. After the induction of anesthesia, the gastric contents were collected via a gastric tube to measure gastric volume and pH. Neither gastric volume nor pH differed between the groups (ORT 9.6 ± 8.2 ml and 5.6 ± 1.7, respectively, vs. standard fasting 8.5 ± 6.8 ml and 5.5 ± 1.7, respectively). These data suggest that ORT may not reduce gastric volume in patients receiving a preanesthetic H(2) antagonist.

[A case of successful tracheal tube exchange with Airway Scope for tube damage during maxillo-mandibular osteotomy].

We report a case of surgical vertical-section of the nasoendotracheal tube during operation, resulting in intra-operative ventilatory difficulties. The patient was a 32-year-old female, scheduled for Maxillo-Mandibular osteotomy under general anesthesia. She was intubated with I.D. 6.0 mm non-kinking tube via left nasal cavity. Forty minutes into a maxillar osteotomy, sudden tracheal tube leak sound was noticed by surgeon. Ten more minutes later, ventilation became difficult, and laryngeal packing was done temporarily. We tried to exchange the nasotracheal tube with Airway Scope, but not with endotracheal tube exchanger, because there was a possibility of complete tube section or difficult extubation from nasal cavity. We could examine the larynx whether it was with edema or not, and two tracheal tubes at the same time. Therefore, we performed tube exchange smoothly and safely. The extubated tracheal tube had serious cut on cuff inflation line made by surgical maneuver. In the case of suspected laryngeal edema or tracheal tube injury, use of Airway Scope for tube exchange may be a safe and reliable method.

Time-consumption risk of real-time ultrasound-guided internal jugular vein cannulation in pediatric patients: comparison with two conventional techniques.

To assess the efficacy of three different methods for internal jugular vein (IJV) cannulation in pediatric patients, we conducted a review of patients undergoing cardiovascular surgery over an 11-year period, in which success rates for cannulation and time from induction of anesthesia to cannulation were evaluated. The success rate was better for real-time ultrasound guidance (USG: 90%) than for anatomic landmarks (AL: 76%) or audio-Doppler guidance (ADG: 74%) and the time required was greater for USG (35.0 +/- 13.6 min) than for AL (26.7 +/- 11.2 min) or ADG (29.2 +/- 8.9 min). However, USG resulted in a higher success rate than the other methods with comparable procedure time for smaller-body-weight (<5 kg) patients. Thus real-time USG leads to the highest success rate for IJV cannulation but with a significant time delay, whereas it was the most useful without time delay for the smaller-body-weight subgroup.

[A case of unanticipated postoperative respiratory distress from cancerous pleural effusion].

A 63-year-old woman with a 2-month history of abdominal distension received diagnostic laparotomy under general anesthesia. The chest X-ray one week preoperatively demonstrated slight left pleural effusion, but she did not show any dyspnea on preanesthetic interview. General anesthesia was induced with propofol, ketamine and fentanyl. Sp(O2) decreased after suction of ascites, but it improved with PEEP Spontaneous respiration developped after the operation, but tidal volume was not enough and respiratory pattern was irregular. Train of four was 100%, and bronchofiberscopy had no suspicions findings. The chest X-ray and TEE revealed extended left hemilateral pleural effusion. Seven hundred seventy ml of hemorrhagic pleural fluid was suctioned. Respiratory pattern improved and the endotracheal tube was removed smoothly. We consider that we diagnosed her state only from her subjective symptoms without considering objective symptoms. Besides we had to explain a possibility of a unanticipated serious respiratory distress. In such a case, more accurate and objective diagnostic procedures are required.