Hypotension prediction index for prevention of intraoperative hypotension in patients undergoing general anesthesia: a randomized controlled trial.

BACKGROUND: Intraoperative hypotension is a common side effect of general anesthesia. Here we examined whether the Hypotension Prediction Index (HPI), a novel warning system, reduces the severity and duration of intraoperative hypotension during general anesthesia. METHODS: This randomized controlled trial was conducted in a tertiary referral hospital. We enrolled patients undergoing general anesthesia with invasive arterial monitoring. Patients were randomized 1:1 either to receive hemodynamic management with HPI guidance (intervention) or standard of care (control) treatment. Intraoperative hypotension treatment was initiated at HPI > 85 (intervention) or mean arterial pressure (MAP) < 65 mmHg (control). The primary outcome was hypotension severity, defined as a time-weighted average (TWA) MAP < 65 mmHg. Secondary outcomes were TWA MAP < 60 and < 55 mmHg. RESULTS: Of the 60 patients who completed the study, 30 were in the intervention group and 30 in the control group. The patients' median age was 62 years, and 48 of them were male. The median duration of surgery was 490 min. The median MAP before surgery presented no significant difference between the two groups. The intervention group showed significantly lower median TWA MAP < 65 mmHg than the control group (0.02 [0.003, 0.08] vs. 0.37 [0.20, 0.58], P < 0.001). Findings were similar for TWA MAP < 60 mmHg and < 55 mmHg. The median MAP during surgery was significantly higher in the intervention group than that in the control group (87.54 mmHg vs. 77.92 mmHg, P < 0.001). CONCLUSIONS: HPI guidance appears to be effective in preventing intraoperative hypotension during general anesthesia. Further investigation is needed to assess the impact of HPI on patient outcomes. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04966364); 202105065RINA; Date of registration: July 19, 2021; The recruitment date of the first patient: July 22, 2021.

Perioperative management and outcomes of minimally invasive esophagectomy: case study of a high-volume tertiary center in Taiwan.

BACKGROUND: Mortality and complication rates for surgical esophagectomy remain high despite progress in surgical techniques and perioperative care. Minimally invasive surgery and intraoperative goal-directed fluid management are gaining popularity in Taiwan; however, perioperative complications and short-term outcomes have been rarely reported. In this retrospective study, we analyzed the surgical procedures performed as well as the perioperative outcomes and treatments after esophagectomy in a high-volume medical center in Taiwan. The goals of this study are to compare the complications and the following treatment between different surgical procedures and to analyze if any preoperative coexisting disease and anesthesia conduct might be associated with postoperative complications and hospitalization course. METHODS: We retrospectively reviewed the data of all patients who had undergone esophagectomy and reconstruction in 2015. Patient characteristics, type of surgery performed, method of anesthesia, postoperative hospitalization course, and additional surgical interventions were reviewed and analyzed. RESULTS: In total, 64 patients were included. Among them, 58 patients (90.6%) were reported squamous cell carcinoma, 33 patients (51.6%) received McKeown minimally invasive esophagectomy (MIE), and 20 (31.3%) received Ivor-Lewis MIE. The most common postoperative complications were pulmonary complications (18.7%), such as empyema and pleural effusion, dysrhythmias (14.1%), anastomosis leakage (14.1%), vocal cord paralysis (9.4%), gastric tube stenosis (4.7%), chyle leakage (4.7%), and acute kidney injury (AKI, 4.7%). Twenty-five percent of patients received secondary operative interventions for the aforementioned complications. Postoperative arrhythmia (P=0.042), pulmonary complications (P=0.009), and AKI (P=0.015) were significantly associated with prolonged intensive care unit (ICU) stays. Thirty-day and 90-day mortality rates were 3.1% and 4.7% respectively. Patients with preoperative arrhythmias have a higher risk of developing post-operative dysrhythmia (P=0.013) and lung complications (P=0.036). Patients with an underlying heart disease are at higher risk of post-op AKI (P=0.002) and second surgical intervention (P=0.013). Chronic kidney diseases are associated with post-op dysrhythmia (P=0.013), lung complications (P=0.036) and post-op AKI (P≤0.01). Although McKeown MIE bore a significantly longer surgical time and higher intraoperatively-infused crystalloid than did Ivor Lewis MIE, there were no significant differences regarding postoperative cardiothoracic complications and patient outcomes. CONCLUSIONS: Postoperative outcomes of McKeown MIE and Ivor-Lewis MIE were comparable in our center and short term outcomes were similar to those in previous reports. However, despite neoadjuvant concurrent chemoradiation therapy (CCRT), the use of minimally invasive techniques, and well-controlled anesthesia, the incidence of perioperative complications remains high. Our results suggest that patients with preoperative comorbidity of arrhythmia, heart diseases, and CKD are associated with more common post-operative complications. Furthermore, postoperative dysrhythmias, pulmonary complications, and AKI warrant special anesthetic and surgical care to prevent prolonged ICU stay.

Twenty-years of lung transplantation in Taiwan: Effects of cumulative institutional experience on early outcomes.

BACKGROUND/PURPOSE: Lung transplantation in Taiwan began in 1991, but the experience was limited and diverse in the early years. We examined the cumulative institutional experience of the largest lung transplant cohort in Taiwan. METHODS: A retrospective review of lung transplantations performed at a single institution from December 1995 through August 2016 was conducted. For comparative purposes, the cohort was divided into halves, with an early group (undergoing lung transplantation in the first decade) vs a late group (undergoing lung transplantation in the second decade). Standardized donor selection, organ procurement, and preservation protocols for brain-dead donors were applied. The outcomes measured were 30-day mortality and actuarial survival using the Kaplan-Meier method. RESULTS: The cohort included 50 recipients in the early group and 42 recipients in the late group. Compared with the early group, recipients in the late group were significantly older (38.8 ± 11.6 vs 44.8 ± 13.4 years, p = 0.024) and more of them required mechanical ventilation before transplant (26.0% vs 66.7%, p < 0.001). There were more female donors (12.0% vs 33.3%, p = 0.021) and gender-matched donors (34.0% vs 61.9%, p = 0.012) in the late group. A total of 87 recipients (94.6%) had cardiopulmonary bypass (CPB) or extracorporeal membrane oxygenation (ECMO) support during transplant, and CPB was used significantly less in the late group. Graft procedures (14.0% vs 47.6%, p < 0.001), delayed chest closure (0% vs 21.4%, p < 0.001), and early tracheostomy (24.0% vs 52.4%, p = 0.005) were performed more in the late group. The durations of hospital and ICU stays were comparable in both groups, but the 30-day mortality was significantly lower in the late group (30.0% vs 2.4%, p = 0.001). CONCLUSION: Although the results were undesirable in the first decade of the transplant program, the cumulative institutional experience led to significantly improved outcomes in the second decade of the transplant program.

A new method to derive fetal heart rate from maternal abdominal electrocardiogram: monitoring fetal heart rate during cesarean section.

BACKGROUND: Monitoring of fetal heart rate (FHR) is important during labor since it is a sensitive marker to obtain significant information about fetal condition. To take immediate response during cesarean section (CS), we noninvasively derive FHR from maternal abdominal ECG. METHODS: We recruited 17 pregnant women delivered by elective cesarean section, with abdominal ECG obtained before and during the entire CS. First, a QRS-template is created by averaging all the maternal ECG heart beats. Then, Hilbert transform was applied to QRS-template to generate the other basis which is orthogonal to the QRS-template. Second, maternal QRS, P and T waves were adaptively subtracted from the composited ECG. Third, Gabor transformation was applied to obtain time-frequency spectrogram of FHR. Heart rate variability (HRV) parameters including standard deviation of normal-to-normal intervals (SDNN), 0V, 1V, 2V derived from symbolic dynamics of HRV and SD1, SD2 derived from Poincareé plot. Three emphasized stages includes: (1) before anesthesia, (2) 5 minutes after anesthesia and (3) 5 minutes before CS delivery. RESULTS: FHRs were successfully derived from all maternal abdominal ECGs. FHR increased 5 minutes after anesthesia and 5 minutes before delivery. As for HRV parameters, SDNN increased both 5 minutes after anesthesia and 5 minutes before delivery (21.30±9.05 vs. 13.01±6.89, P < 0.001 and 22.88±12.01 vs. 13.01±6.89, P < 0.05). SD1 did not change during anesthesia, while SD2 increased significantly 5 minutes after anesthesia (27.92±12.28 vs. 16.18±10.01, P < 0.001) and both SD2 and 0V percentage increased significantly 5 minutes before delivery (30.54±15.88 vs. 16.18±10.01, P < 0.05; 0.39±0.14 vs. 0.30±0.13, P < 0.05). CONCLUSIONS: We developed a novel method to automatically derive FHR from maternal abdominal ECGs and proved that it is feasible during CS.

Influence of morphine on host immunity.

Morphine is a widely used drug for analgesia and substance abuse. It has been accepted as a safe medication with great analgesic efficacy. Previous studies have reported that morphine is highly associated with the risk of immunosuppressive effects. Although the observed clinical effects suggest that morphine has the immunomodulatory capabilities, the mechanism of its action is still unclear. Here we review morphine on the bench to improve our understanding of the drug on the host immunity at the bedside. Studies of the effects of morphine on the innate and adaptive immune systems as well as immune responses are also discussed.

Morphine induces apoptosis of human endothelial cells through nitric oxide and reactive oxygen species pathways.

Morphine has been widely used for pain management. Other than analgesia, it has effects on vascular endothelial cells, including angiogenesis and apoptosis. An in vitro model of human umbilical vein endothelial cells (HUVECs) was made to investigate the effects and comprehensive mechanisms of morphine on vascular endothelial cells. Morphine enhanced apoptosis of HUVECs, increased intracellular reactive oxygen species (ROS), and reduced mitochondrial membrane potentials (MMPs). It also induced the release of NO and activated NF-kappaB in HUVECs. Naloxone, the opioid receptor antagonist, could reverse cell apoptosis and ROS generation, NO production, and MMP loss. Expression levels of Bak and Bax, and the activation of caspases 3 and 7 in HUVECs significantly increased when treated with morphine. Inhibition of NO production by NO synthase inhibitor reduced morphine-induced apoptosis. Morphine could induce apoptosis of HUVECs through both the NO and ROS pathways. Thus, inhibiting NO or ROS may be a potential target in blocking morphine-induced apoptosis of endothelial cells.

Induction of hepatic glutathione S-transferase and UDP-glucuronosyltransferase activities by ketamine in rats.

BACKGROUND: Ketamine has been shown to induce rat cytochrome P-450 in a way similar to phenobarbital. However, whether ketamine is able to induce glutathione S-transferase (GST) and UDP-glucuronosyltransferase (UGT), two major phase II drug-metabolizing enzymes, remains unclear. The present study aimed to investigate the effect of ketamine on GST and UGT activities in rats. METHODS: In a dose-response study, male adult Wistar rats were treated with 10, 20, 40 or 80 mg/kg ketamine intraperitoneally twice daily for 4 days. Livers were removed 1 day after ketamine treatment and hepatic GST and UGT activities were determined. In a reversibility study, rats were treated with 80 mg/kg ketamine intraperitoneally twice daily for 4 days and killed 1, 2, 3 or 4 days after the last dose of ketamine. Livers were removed and hepatic GST and UGT activities were determined. RESULTS: The results of the dose-response study showed that treatment of rats with 10, 20, 40, or 80 mg/kg ketamine produced 19%, 20%, 18%, and 25% increases respectively in the catalytic activity of hepatic cytosolic GST, and 41%, 41%, 35%, and 38% increases respectively in the catalytic activity of microsomal UGT. The results of the reversibility study showed that the GST activities of the rats killed 1, 2, 3, or 4 days after ketamine treatment were 62%, 88%, 46% and 65% higher than the activity of the control group. The UGT activities of the rats killed 1, 2, 3, or 4 days after ketamine treatment were 56%, 53%, 54% and 72% higher than the activity of the control group. CONCLUSION: Ketamine is able to induce the activities of hepatic GST and UGT in rats. The induced GST and UGT activities persist for at least 4 days after cessation of ketamine. The results suggest the possibility of interactions of drugs related to phase II enzyme induction in chronic ketamine users.

Chimeric DNA vaccine reverses morphine-induced immunosuppression and tumorigenesis.

Although long-term use of morphine has been shown to promote tumor growth, the question whether tumorigenesis occurs as a result of an immunosuppressive effect remains to be investigated. In mice rendered tolerant to morphine, the efficacy and mechanism of a vaccination to rescue morphine-induced immunosuppression and prevent tumor growth was assessed both in vitro and in vivo. Herein, we found that morphine-injected mice exhibited higher tumor growth rates and lower percentages of CD8+ T lymphocytes. The mechanism of morphine suppression of immunity might be through the suppression of E7-specific CD8+ T lymphocyte proliferation and the promotion of apoptosis of these cells by the Bcl-2 and Bax pathways. The suppressive effect of E7-specific CD8+ T lymphocytes by morphine could be reversed by naloxone. We have previously shown that calreticulin linked with E7 (CRT/E7) could enhance the CD8+ T cell response and the anti-tumor effects (W. F. Cheng et al. (2001) J. Clin. Invest. 108, 669-678). CRT/E7 DNA vaccine could overcome the immunosuppressive effect of morphine and suppress tumor growth. Our findings reveal that long-term morphine treatment dose-dependently promotes tumor growth and a DNA vaccine may serve as a useful approach to treat the profound immunosuppressive function and prevent tumorigenesis after long-term morphine treatment.

Immunoneutralization of c-Fos using intrathecal antibody electroporation attenuates chronic constrictive injury-induced hyperalgesia and regulates preprodynorphin expression in rats.

BACKGROUND: In vivo electroporation has been successfully used for the introduction of DNA, RNA, oligonucleotides, and proteins into cells for experimental and therapeutic purposes. The authors evaluated the efficacy of electroporation-mediated c-Fos antibody therapy for neuropathic pain in vitro and in vivo. METHODS: First, the authors studied the inhibitory effects of intrathecal c-Fos antibody electroporation on the activating protein (AP-1) promoter activity in cultured spinal neuronal cells transfected with p-AP-Luc plasmid and activated with 100 microm glutamate. The inhibitory effect of c-Fos antibody electroporation in the regulation of AP-1 promoter activity was assessed according to the relative luciferase activity. Second, rats with chronic constrictive injury underwent electroporation treatment for neuropathic pain using c-Fos antibody. Thermal nociceptive thresholds were measured before chronic constrictive injury and then on even-numbered days, up to and including day 14, to assess and compare the therapeutic effects of intrathecal electroporation. The time course was assessed by Western blot analysis and by immunohistochemical analysis. Pronociceptive gene expression was measured by assessing prodynorphin mRNA and dynorphin peptides on days 2 and 10 after intrathecal c-Fos electroporation. RESULTS: Cotransfection of c-Fos antibody significantly decreased glutamate-induced AP-1 activity. Intrathecal electrotransfer of c-Fos antibody attenuated spinal dynorphin levels, as manifested by significantly elevated pain thresholds in the chronic constrictive injury-affected limbs. CONCLUSION: This study shows that transfer of antibody into rat spinal cords by intrathecal electroporation is a useful method to study the function of endogenous factors of spinal-related disorders.

Right upper lobe pulmonary edema after mitral valve replacement caused by paravalvular leakage recognized by bedside transesophageal echocardiography.

OBJECTIVE: To describe an unusual case of right upper lobe pulmonary edema caused by acute paravalvular leakage that was identified by the use of bedside transesophageal echocardiography. DESIGN: Case report. SETTING: University-affiliated hospital. PATIENT: A 59-yr-old male patient underwent prosthetic mitral valve replacement (St. Jude valve) for severe mitral regurgitation and developed sudden onset of dyspnea and change in consciousness with blood pressure decreased to 70/30 mm Hg. Elevation of central venous pressure and images of transthoracic echocardiography led to the diagnosis of cardiac tamponade. CONCLUSION: Acute paravalvular leakage after mitral valvular replacement should be considered as one of the differential diagnoses for unilateral pulmonary edema. Physical findings of a holosystolic murmur and findings from bedside transesophageal echocardiography can confirm the diagnosis, avoiding delay in management.